36 results on '"Andrew Orry"'
Search Results
2. Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin
- Author
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Felix Blei, Janis Fricke, Andreas Naschberger, Andrew Orry, Alexander M. Sherwood, Bernhard Rupp, Robert B. Kargbo, and Dirk Hoffmeister
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S-Adenosylmethionine ,Indoles ,Psilocybe cubensis ,In silico ,010402 general chemistry ,Methylation ,01 natural sciences ,Biochemistry ,Psilocybin ,Fungal Proteins ,chemistry.chemical_compound ,Alkaloids ,Bacterial Proteins ,Biosynthesis ,Tryptophan Synthase ,medicine ,Molecular Biology ,Indole test ,chemistry.chemical_classification ,Psilocybe ,Molecular Structure ,biology ,010405 organic chemistry ,Organic Chemistry ,Salmonella enterica ,Methyltransferases ,biology.organism_classification ,Organophosphates ,0104 chemical sciences ,Molecular Docking Simulation ,Baeocystin ,Enzyme ,chemistry ,Molecular Medicine ,Protein Binding ,medicine.drug - Abstract
Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6-methylated psilocybin and baeocystin from 4-hydroxy-6-methyl-l-tryptophan, which was decarboxylated and phosphorylated by the Psilocybe cubensis biosynthesis enzymes PsiD and PsiK. N-Methylation was catalyzed by PsiM. We further present an in silico structural model of PsiM that revealed a well-conserved SAM-binding core along with peripheral nonconserved elements that likely govern substrate preferences.
- Published
- 2019
3. Purification, kinetic characterization, and site-directed mutagenesis of Methanothermobacter thermautotrophicus RFAP Synthase Produced in Escherichia coli
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Andrew Orry, Dina Greene, Anna Pham, Madeline E. Rasche, Matthew E. Bechard, and Payam Farahani
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Microbiology (medical) ,chemistry.chemical_classification ,Alanine ,0303 health sciences ,biology ,ATP synthase ,Homoserine kinase ,030303 biophysics ,Active site ,Microbiology ,Amino acid ,03 medical and health sciences ,chemistry.chemical_compound ,Biochemistry ,Biosynthesis ,chemistry ,13. Climate action ,biology.protein ,Binding site ,Site-directed mutagenesis ,030304 developmental biology - Abstract
Methane-producing archaea are among a select group of microorganisms that utilize tetrahydromethanopterin (H4MPT) as a one-carbon carrier instead of tetrahydrofolate. In H4MPT biosynthesis, β-ribofuranosylaminobenzene 5’-phosphate (RFAP) synthase catalyzes the production of RFAP, CO2, and pyrophosphate from p-aminobenzoic acid (pABA) and phosphoribosyl-pyrophosphate (PRPP). In this work, to gain insight into amino acid residues required for substrate binding, RFAP synthase from Methanothermobacter thermautotrophicus was produced in Escherichia coli, and site-directed mutagenesis was used to alter arginine 26 (R26) and aspartic acid 19 (D19), located in a conserved sequence of amino acids resembling the pABA binding site of dihydropteroate synthase. Replacement of R26 with lysine increased the KM for pABA by an order of magnitude relative to wild-type enzyme without substantially altering the KM for PRPP. Although replacement of D19 with alanine produced inactive enzyme, asparagine substitution allowed retention of some activity, and the KM for pABA increased about threefold relative to wild-type enzyme. A molecular model developed by threading RFAP synthase onto the crystal structure of homoserine kinase places R26 in the proposed active site. In the static model, D19 is located close to the active site, yet appears too far away to influence ligand binding directly. This may be indicative of the protein conformational change predicted previously in the Bi-Ter kinetic mechanism and/or formation of the active site at the interface of two subunits. Due to the vital role of RFAP synthase in H4MPT biosynthesis, insights into the mode of substrate binding and mechanism could be beneficial for developing RFAP synthase inhibitors designed to reduce the production of methane as a greenhouse gas.
- Published
- 2019
4. Targeting the Cyclophilin Domain of Ran-binding Protein 2 (Ranbp2) with Novel Small Molecules to Control the Proteostasis of STAT3, hnRNPA2B1 and M-Opsin
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Se Eun Park, Andrew Orry, Kyoung-in Cho, and Paulo Ademar Avelar Ferreira
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STAT3 Transcription Factor ,Heterogeneous nuclear ribonucleoprotein ,Physiology ,Cognitive Neuroscience ,Molecular Sequence Data ,Cypa ,Ligands ,Biochemistry ,Article ,Cyclophilin A ,Heterogeneous-Nuclear Ribonucleoprotein Group A-B ,Humans ,Amino Acid Sequence ,Cyclophilin ,Molecular Structure ,Opsins ,Sequence Homology, Amino Acid ,biology ,Drug discovery ,Cell Biology ,General Medicine ,biology.organism_classification ,Cell biology ,Nuclear Pore Complex Proteins ,Proteostasis ,Chaperone (protein) ,biology.protein ,RANBP2 ,HeLa Cells ,Molecular Chaperones - Abstract
Cyclophilins are peptidyl cis-trans prolyl isomerases (PPIases), whose activity is typically inhibited by cyclosporine A (CsA), a potent immunosuppressor. Cyclophilins are also chaperones. Emerging evidence supports that cyclophilins present non-overlapping PPIase and chaperone activities. The proteostasis of the disease-relevant substrates, signal transducer and activator of transcription 3 and 5 (STAT3/STAT5), heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and M-opsin, are regulated by non-overlapping chaperone and PPIase activities of the cyclophilin domain (CY) of Ranbp2, a multifunctional and modular scaffold which controls nucleocytoplasmic shuttling and proteostasis of selective substrates. Although highly homologous, CY and the archetypal cyclophilin A (CyPA) present distinct catalytic and CsA-binding activities owing to unique structural features between these cylophilins. We explored structural idiosyncrasies between CY and CyPA to screen in silico nearly 9 million small molecules (SM) against the CY PPIase pocket and identify SMs with selective bioactivity toward STAT3, hnRNPA2B1 and/or M-opsin proteostasis. We found three classes of SMs that enhance the cytokine-stimulated transcriptional activity of STAT3 without changing latent and activated STAT3 levels, down-regulate hnRNPA2B1 or M-opsin proteostasis, or a combination of these. Further, a SM which suppresses hnRNPA2B1 proteostasis also inhibits strongly and selectively the PPIase activity of CY. This study unravels chemical probes for multimodal regulation of CY of Ranbp2 and its substrates and this regulation likely results in the allosterism stemming from the interconversion of conformational substates of cyclophilins. The results also demonstrate the feasibility of CY in drug discovery against disease-relevant substrates controlled by Ranbp2 and they open new opportunities for therapeutic interventions.
- Published
- 2015
5. Differential Loss of Prolyl Isomerase or Chaperone Activity of Ran-binding Protein 2 (Ranbp2) Unveils Distinct Physiological Roles of Its Cyclophilin Domain in Proteostasis
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Eugene Senda, Dosuk Yoon, Kyoung In Cho, Paulo Ademar Avelar Ferreira, Minzhong Yu, Sunny Qiu, Andrew Orry, Hemangi Patil, Jessica Wang, Neal S. Peachey, and Haiqing Yi
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Aging ,Protein Folding ,GTPase-activating protein ,Down-Regulation ,Biochemistry ,Histone Deacetylases ,Mice ,Structure-Activity Relationship ,Immunophilins ,Heterogeneous-Nuclear Ribonucleoprotein Group A-B ,polycyclic compounds ,Prolyl isomerase ,Animals ,Humans ,Protein Structure, Quaternary ,Molecular Biology ,Cyclophilin ,Peptidylprolyl isomerase ,Opsins ,biology ,Ubiquitin ,GTPase-Activating Proteins ,Cell Biology ,Peptidylprolyl Isomerase ,Protein Structure, Tertiary ,Nuclear Pore Complex Proteins ,enzymes and coenzymes (carbohydrates) ,Protein Transport ,STAT Transcription Factors ,Proteostasis ,Organ Specificity ,Protein Synthesis and Degradation ,Chaperone (protein) ,Mutation ,cardiovascular system ,Biocatalysis ,Retinal Cone Photoreceptor Cells ,Small Ubiquitin-Related Modifier Proteins ,biology.protein ,Evoked Potentials, Visual ,Mutant Proteins ,RANBP2 ,HeLa Cells ,Molecular Chaperones - Abstract
The immunophilins, cyclophilins, catalyze peptidyl cis-trans prolyl-isomerization (PPIase), a rate-limiting step in protein folding and a conformational switch in protein function. Cyclophilins are also chaperones. Noncatalytic mutations affecting the only cyclophilins with known but distinct physiological substrates, the Drosophila NinaA and its mammalian homolog, cyclophilin-B, impair opsin biogenesis and cause osteogenesis imperfecta, respectively. However, the physiological roles and substrates of most cyclophilins remain unknown. It is also unclear if PPIase and chaperone activities reflect distinct cyclophilin properties. To elucidate the physiological idiosyncrasy stemming from potential cyclophilin functions, we generated mice lacking endogenous Ran-binding protein-2 (Ranbp2) and expressing bacterial artificial chromosomes of Ranbp2 with impaired C-terminal chaperone and with (Tg-Ranbp2(WT-HA)) or without PPIase activities (Tg-Ranbp2(R2944A-HA)). The transgenic lines exhibit unique effects in proteostasis. Either line presents selective deficits in M-opsin biogenesis with its accumulation and aggregation in cone photoreceptors but without proteostatic impairment of two novel Ranbp2 cyclophilin partners, the cytokine-responsive effectors, STAT3/STAT5. Stress-induced STAT3 activation is also unaffected in Tg-Ranbp2(R2944A-HA)::Ranbp2(-/-). Conversely, proteomic analyses found that the multisystem proteinopathy/amyotrophic lateral sclerosis proteins, heterogeneous nuclear ribonucleoproteins A2/B1, are down-regulated post-transcriptionally only in Tg-Ranbp2(R2944A-HA)::Ranbp2(-/-). This is accompanied by the age- and tissue-dependent reductions of diubiquitin and ubiquitylated proteins, increased deubiquitylation activity, and accumulation of the 26 S proteasome subunits S1 and S5b. These manifestations are absent in another line, Tg-Ranbp2(CLDm-HA)::Ranbp2(-/-), harboring SUMO-1 and S1-binding mutations in the Ranbp2 cyclophilin-like domain. These results unveil distinct mechanistic and biological links between PPIase and chaperone activities of Ranbp2 cyclophilin toward proteostasis of selective substrates and with novel therapeutic potential.
- Published
- 2014
6. Molecular Basis for Benzodiazepine Agonist Action at the Type 1 Cholecystokinin Receptor
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Polo C.-H. Lam, Erin E. Cawston, Ruben Abagyan, Arthur Christopoulos, Brad R. Henke, Achyut Patil, Andrew Orry, Kaleeckal G. Harikumar, Laurence J. Miller, and Patrick M. Sexton
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Models, Molecular ,Agonist ,medicine.drug_class ,Molecular Sequence Data ,Allosteric regulation ,CHO Cells ,digestive system ,Biochemistry ,Cholecystokinin receptor ,Benzodiazepines ,Cricetulus ,Cricetinae ,medicine ,Animals ,Amino Acid Sequence ,Receptor ,Molecular Biology ,Cholecystokinin ,Chemistry ,digestive, oral, and skin physiology ,Biological activity ,Cell Biology ,Small molecule ,Receptor, Cholecystokinin B ,Recombinant Proteins ,Receptor, Cholecystokinin A ,ROC Curve ,Docking (molecular) ,Mutant Proteins ,Sequence Alignment ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction - Abstract
Understanding the molecular basis of drug action can facilitate development of more potent and selective drugs. Here, we explore the molecular basis for action of a unique small molecule ligand that is a type 1 cholecystokinin (CCK) receptor agonist and type 2 CCK receptor antagonist, GI181771X. We characterize its binding utilizing structurally related radioiodinated ligands selective for CCK receptor subtypes that utilize the same allosteric ligand-binding pocket, using wild-type receptors and chimeric constructs exchanging the distinct residues lining this pocket. Intracellular calcium assays were performed to determine biological activity. Molecular models for docking small molecule agonists to the type 1 CCK receptor were developed using a ligand-guided refinement approach. The optimal model was distinct from the previous antagonist model for the same receptor and was mechanistically consistent with the current mutagenesis data. This study revealed a key role for Leu(7.39) that was predicted to interact with the isopropyl group in the N1 position of the benzodiazepine that acts as a "trigger" for biological activity. The molecular model was predictive of binding of other small molecule agonists, effectively distinguishing these from 1065 approved drug decoys with an area under curve value of 99%. The model also selectively enriched for agonist compounds, with 130 agonists identified by ROC analysis when seeded in 2175 non-agonist ligands of the type 1 CCK receptor (area under curve 78%). Benzodiazepine agonists in this series docked in consistent pose within this pocket, with a key role played by Leu(7.39), whereas the role of this residue was less clear for chemically distinct agonists.
- Published
- 2013
7. Probing the role of the N‐terminus in the ADP‐Glucose Pyrophosphorylase from Thermodesulfovibrio yellowstonii
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Eric Yik, Christopher R Meyer, Jackson Nguyen, Dylan Campbell, Casey Diep, Andrew Orry, Nicholas Duran, and Edward Pushkarev
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N-terminus ,Thermodesulfovibrio yellowstonii ,Biochemistry ,Chemistry ,Genetics ,ADP Glucose ,Molecular Biology ,Biotechnology - Published
- 2016
8. Structure‐Function Studies of Deinococcus radiodurans ADP Glucose Pyrophosphorylase: Role of Ser48 in Allosteric Regulation
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Jeries Qoborsi, Andrew Orry, Christopher R Meyer, Leo Ong, and Ashley Le‐Pham
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Biochemistry ,biology ,Chemistry ,Structure function ,Allosteric regulation ,Genetics ,ADP Glucose ,Deinococcus radiodurans ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2016
9. Structure‐Function Studies of the Thermotoga maritima ADPGlucose Pyrophosphorylase: Probing the role of the C‐terminus of the GlgD subunit
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Jan Tiet, Andrea Kuipers, Crystal Vu, Andrew Orry, and Christopher R Meyer
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2016
10. Use of Cysteine Trapping to Map Spatial Approximations between Residues Contributing to the Helix N-capping Motif of Secretin and Distinct Residues within Each of the Extracellular Loops of Its Receptor
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Patrick M. Sexton, Andrew Orry, Laurence J. Miller, Polo C.-H. Lam, Ruben Abagyan, Maoqing Dong, and Arthur Christopoulos
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0301 basic medicine ,Amino Acid Motifs ,cell surface receptor ,Peptide ,Plasma protein binding ,Ligand Binding Protein ,Biochemistry ,Medical and Health Sciences ,Receptors, G-Protein-Coupled ,gel electrophoresis ,Cricetinae ,Receptors ,Chlorocebus aethiops ,Cyclic AMP ,membrane protein ,Peptide sequence ,chemistry.chemical_classification ,Gastrointestinal Hormone ,Biological Sciences ,Ligand (biochemistry) ,ligand-binding protein ,Protein Structure and Folding ,COS Cells ,mutagenesis ,Protein Binding ,Biochemistry & Molecular Biology ,Stereochemistry ,1.1 Normal biological development and functioning ,Molecular Sequence Data ,CHO Cells ,Receptors, Gastrointestinal Hormone ,03 medical and health sciences ,G-Protein-Coupled ,Cricetulus ,Secretin ,Underpinning research ,Animals ,Humans ,Cysteine ,Amino Acid Sequence ,G protein-coupled receptor ,Binding site ,Molecular Biology ,Binding selectivity ,Binding Sites ,030102 biochemistry & molecular biology ,molecular modeling ,Cell Biology ,030104 developmental biology ,chemistry ,Chemical Sciences ,peptides ,Alpha helix - Abstract
Amino-terminal regions of secretin-family peptides contain key determinants for biological activity and binding specificity, although the nature of interactions with receptors is unclear. A helix N-capping motif within this region has been postulated to directly contribute to agonist activity while also stabilizing formation of a helix extending toward the peptide carboxyl terminus and docking within the receptor amino terminus. We used cysteine trapping to systematically explore spatial approximations between cysteines replacing each residue in this motif of secretin (sec), Phe(6), Thr(7), and Leu(10), and cysteines incorporated into the extracellular face of the receptor. Each peptide was a full agonist for cAMP, but had a lower binding affinity than natural hormone. These bound to COS cells expressing 61 receptor constructs incorporating cysteines in every position along each extracellular loop (ECL) and adjacent parts of transmembrane (TM) segments. Patterns of covalent labeling were distinct for each probe, with Cys(6)-sec labeling multiple residues in the carboxyl-terminal half of ECL2 and throughout ECL3, Cys(7)-sec predominantly labeling only single residues in the carboxyl-terminal end of ECL2 and the amino-terminal end of ECL3, and Cys(10)-sec not efficiently labeling any of these residues. These spatial constraints were used to refine our model of secretin bound to its receptor, now bringing ECL3 above the amino terminus of the ligand and revealing possible charge-charge interactions between this part of secretin and receptor residues in TM5, TM6, ECL2, and ECL3, which can orient and stabilize the peptide-receptor complex. This was validated by testing predicted approximations by mutagenesis and residue-residue complementation studies.
- Published
- 2016
11. Molecular Basis for Binding and Subtype Selectivity of 1,4-Benzodiazepine Antagonist Ligands of the Cholecystokinin Receptor
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Andrew Orry, Erin E. Cawston, Mary Lou Augustine, Polo C.-H. Lam, Patrick M. Sexton, Ruben Abagyan, Eyup Akgün, Philip S. Portoghese, Maoqing Dong, Alicja M. Ball, Kaleeckal G. Harikumar, and Laurence J. Miller
- Subjects
Stereochemistry ,Molecular Sequence Data ,Allosteric regulation ,Peptide binding ,Ligands ,digestive system ,Biochemistry ,Cholecystokinin receptor ,Benzodiazepines ,Chlorocebus aethiops ,Animals ,Amino Acid Sequence ,Homology modeling ,Receptor ,Molecular Biology ,Sequence Homology, Amino Acid ,Ligand ,Chemistry ,digestive, oral, and skin physiology ,Cell Biology ,Small molecule ,Docking (molecular) ,COS Cells ,Receptors, Cholecystokinin ,hormones, hormone substitutes, and hormone antagonists ,Allosteric Site ,Signal Transduction - Abstract
Allosteric binding pockets in peptide-binding G protein-coupled receptors create opportunities for the development of small molecule drugs with substantial benefits over orthosteric ligands. To gain insights into molecular determinants for this pocket within type 1 and 2 cholecystokinin receptors (CCK1R and CCK2R), we prepared a series of receptor constructs in which six distinct residues in TM2, -3, -6, and -7 were reversed. Two novel iodinated CCK1R- and CCK2R-selective 1,4-benzodiazepine antagonists, differing only in stereochemistry at C3, were used. When all six residues within CCK1R were mutated to corresponding CCK2R residues, benzodiazepine selectivity was reversed, yet peptide binding selectivity was unaffected. Detailed analysis, including observations of gain of function, demonstrated that residues 6.51, 6.52, and 7.39 were most important for binding the CCK1R-selective ligand, whereas residues 2.61 and 7.39 were most important for binding CCK2R-selective ligand, although the effect of substitution of residue 2.61 was likely indirect. Ligand-guided homology modeling was applied to wild type receptors and those reversing benzodiazepine binding selectivity. The models had high predictive power in enriching known receptor-selective ligands from related decoys, indicating a high degree of precision in pocket definition. The benzodiazepines docked in similar poses in both receptors, with C3 urea substituents pointing upward, whereas different stereochemistry at C3 directed the C5 phenyl rings and N1 methyl groups into opposite orientations. The geometry of the binding pockets and specific interactions predicted for ligand docking in these models provide a molecular framework for understanding ligand selectivity at these receptor subtypes. Furthermore, the strong predictive power of these models suggests their usefulness in the discovery of lead compounds and in drug development programs.
- Published
- 2012
12. Molecular Basis of Secretin Docking to Its Intact Receptor Using Multiple Photolabile Probes Distributed throughout the Pharmacophore
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Patrick M. Sexton, Laurence J. Miller, Andrew Orry, Delia I. Pinon, Ruben Abagyan, Keiko Hosohata, Maoqing Dong, and Polo C.-H. Lam
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Receptor complex ,Stereochemistry ,CHO Cells ,Ligand Binding Protein ,Ligands ,Peptide Mapping ,Biochemistry ,Receptors, G-Protein-Coupled ,Receptors, Gastrointestinal Hormone ,Cricetulus ,Secretin ,Cricetinae ,Chlorocebus aethiops ,Animals ,Protein Structure, Quaternary ,Receptor ,Structural motif ,Molecular Biology ,Chemistry ,Cell Biology ,Protein Structure, Tertiary ,Rats ,Docking (molecular) ,Molecular Probes ,Protein Structure and Folding ,COS Cells ,Secretin receptor ,Pharmacophore ,Peptides ,Molecular probe - Abstract
The molecular basis of ligand binding and activation of family B G protein-coupled receptors is not yet clear due to the lack of insight into the structure of intact receptors. Although NMR and crystal structures of amino-terminal domains of several family members support consistency in general structural motifs that include a peptide-binding cleft, there are variations in the details of docking of the carboxyl terminus of peptide ligands within this cleft, and there is no information about siting of the amino terminus of these peptides. There are also no empirical data to orient the receptor amino terminus relative to the core helical bundle domain. Here, we prepared a series of five new probes, incorporating photolabile moieties into positions 2, 15, 20, 24, and 25 of full agonist secretin analogues. Each bound specifically to the receptor and covalently labeled single distinct receptor residues. Peptide mapping of labeled wild-type and mutant receptors identified that the position 15, 20, and 25 probes labeled residues within the distal amino terminus of the receptor, whereas the position 24 probe labeled the amino terminus adjacent to TM1. Of note, the position 2 probe labeled a residue within the first extracellular loop of the receptor, a region not previously labeled, providing an important new constraint for docking the amino-terminal region of secretin to its receptor core. These additional experimentally derived constraints help to refine our understanding of the structure of the secretin-intact receptor complex and provide new insights into understanding the molecular mechanism for activation of family B G protein-coupled receptors.
- Published
- 2011
13. Secretin Occupies a Single Protomer of the Homodimeric Secretin Receptor Complex
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Patrick M. Sexton, Delia I. Pinon, Laurence J. Miller, Andrew Orry, Ruben Abagyan, Polo C.-H. Lam, and Maoqing Dong
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Receptor complex ,Molecular model ,Photoaffinity labeling ,Cooperative binding ,Cell Biology ,Protomer ,Biology ,Biochemistry ,Secretin ,Biophysics ,Secretin receptor ,Receptor ,Molecular Biology - Abstract
The secretin receptor, a prototypic family B G protein-coupled receptor, forms a constitutive homodimeric complex that is stable even in the presence of hormone. Recently, a model of this agonist-bound receptor was built based on high resolution structures reported for amino-terminal domains of other family members. Although this model provided the best solution for all extant data, including 10 photoaffinity labeling constraints, a new such constraint now obtained with a position 16 photolabile probe was inconsistent with this model. As the secretin receptor forms constitutive homodimers, we explored whether secretin might dock across both protomers of the complex, an observation that could also contribute to the negative cooperativity observed. To directly explore this, we prepared six secretin analogue probes that simultaneously incorporated two photolabile benzoylphenylalanines as sites of covalent attachment, in positions known to label distinct receptor subdomains. Each bifunctional probe was a full agonist that labeled the receptor specifically and saturably, with electrophoretic migration consistent with labeling a single protomer of the homodimeric secretin receptor. No band representing radiolabeled receptor dimer was observed with any bifunctional probe. The labeled monomeric receptor bands were cleaved with cyanogen bromide to demonstrate that both of the photolabile benzoylphenylalanines within a single probe had established covalent adducts with a single receptor in the complex. These data are consistent with a model of secretin occupying a single secretin receptor protomer within the homodimeric receptor complex. A new molecular model accommodating all constraints is now proposed.
- Published
- 2010
14. Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport
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Martin Haslbeck, Daniele Seppi, Andreas Naschberger, Didier Nurizzo, Matthew W. Bowler, Andrew Orry, Markus A. Keller, Hans Dieplinger, Gregor Oemer, Stefan Lechner, Bernhard Rupp, Mislav Novokmet, and Kathrin Pansi
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0301 basic medicine ,Cell signaling ,Glycosylation ,Lipoylation ,Serum Albumin, Human ,Biology ,Serine ,03 medical and health sciences ,chemistry.chemical_compound ,Structural Biology ,Wnt3A Protein ,Humans ,Homology modeling ,Molecular Biology ,Glycoproteins ,chemistry.chemical_classification ,Binding Sites ,030102 biochemistry & molecular biology ,Protein Stability ,Wnt signaling pathway ,Acetylation ,Transport protein ,Molecular Docking Simulation ,Protein Transport ,afamin crystal structure plasma glycoprotein lipid transport glycosylation Wnt proteins Wnt3a-afamin complex model cell signaling acylation ,030104 developmental biology ,Biochemistry ,chemistry ,Chaperone (protein) ,biology.protein ,Carrier Proteins ,Glycoprotein ,Protein Processing, Post-Translational ,Protein Binding - Abstract
Afamin, a human plasma glycoprotein and putative transporter of hydrophobic molecules, has been shown to act as extracellular chaperone for poorly soluble, acylated Wnt proteins, forming a stable, soluble complex with functioning Wnt proteins. The 2.1-Å crystal structure of glycosylated human afamin reveals an almost exclusively hydrophobic binding cleft capable of harboring large hydrophobic moieties. Lipid analysis confirms the presence of lipids, and density in the primary binding pocket of afamin was modeled as palmitoleic acid, presenting the native O-acylation on serine 209 in human Wnt3a. The modeled complex between the experimental afamin structure and a Wnt3a homology model based on the XWnt8-Fz8-CRD fragment complex crystal structure is compelling, with favorable interactions comparable with the crystal structure complex. Afamin readily accommodates the conserved palmitoylated serine 209 of Wnt3a, providing a structural basis how afamin solubilizes hydrophobic and poorly soluble Wnt proteins.
- Published
- 2017
15. Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Structure-Based Virtual Screening
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Marybeth S. Burton, Marvin L. Bayne, Sue Ann Kocsi, Kim A. O’Neill, Ruben Abagyan, Michael F. Czarniecki, Frederick J. Monsma, Brian E. Hawes, Andrew Orry, Nicholas J. Murgolo, Johannes H. Voigt, Heather Hine, and Claudio N. Cavasotto
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Models, Molecular ,Rhodopsin ,Databases, Factual ,Molecular model ,CHO Cells ,Ligands ,Binding, Competitive ,Structure-Activity Relationship ,Cricetulus ,Cricetinae ,Drug Discovery ,Animals ,Humans ,Structure–activity relationship ,Receptors, Pituitary Hormone ,Receptors, Somatostatin ,Homology modeling ,Binding site ,G protein-coupled receptor ,Stochastic Processes ,Virtual screening ,Binding Sites ,Sequence Homology, Amino Acid ,biology ,Chemistry ,Biochemistry ,Docking (molecular) ,biology.protein ,Thermodynamics ,Molecular Medicine ,Cattle ,hormones, hormone substitutes, and hormone antagonists - Abstract
Melanin-concentrating hormone receptor 1 (MCH-R1) is a G-protein-coupled receptor (GPCR) and a target for the development of therapeutics for obesity. The structure-based development of MCH-R1 and other GPCR antagonists is hampered by the lack of an available experimentally determined atomic structure. A ligand-steered homology modeling approach has been developed (where information about existing ligands is used explicitly to shape and optimize the binding site) followed by docking-based virtual screening. Top scoring compounds identified virtually were tested experimentally in an MCH-R1 competitive binding assay, and six novel chemotypes as low micromolar affinity antagonist "hits" were identified. This success rate is more than a 10-fold improvement over random high-throughput screening, which supports our ligand-steered method. Clearly, the ligand-steered homology modeling method reduces the uncertainty of structure modeling for difficult targets like GPCRs.
- Published
- 2008
16. Structure-based identification of binding sites, native ligands and potential inhibitors for G-protein coupled receptors
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Ruben Abagyan, Andrew Orry, and Claudio N. Cavasotto
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Models, Molecular ,Rhodopsin ,Binding Sites ,Stereochemistry ,Membrane Proteins ,Drug design ,Receptors, Cell Surface ,Plasma protein binding ,Biology ,Ligands ,Biochemistry ,Protein Structure, Tertiary ,Protein structure ,Protein–ligand docking ,GTP-Binding Proteins ,Structural Biology ,Docking (molecular) ,Searching the conformational space for docking ,Bacteriorhodopsins ,Animals ,Cattle ,Binding site ,Molecular Biology ,Protein Binding ,G protein-coupled receptor - Abstract
G-protein coupled receptors (GPCRs) are the largest family of cell-surface receptors involved in signal transmission. Drugs associated with GPCRs represent more than one fourth of the 100 top-selling drugs and are the targets of more than half of the current therapeutic agents on the market. Our methodology based on the internal coordinate mechanics (ICM) program can accurately identify the ligand-binding pocket in the currently available crystal structures of seven transmembrane (7TM) proteins [bacteriorhodopsin (BR) and bovine rhodopsin (bRho)]. The binding geometry of the ligand can be accurately predicted by ICM flexible docking with and without the loop regions, a useful finding for GPCR docking because the transmembrane regions are easier to model. We also demonstrate that the native ligand can be identified by flexible docking and scoring in 1.5% and 0.2% (for bRho and BR, respectively) of the best scoring compounds from two different types of compound database. The same procedure can be applied to the database of available chemicals to identify specific GPCR binders. Finally, we demonstrate that even if the sidechain positions in the bRho binding pocket are entirely wrong, their correct conformation can be fully restored with high accuracy (0.28 A) through the ICM global optimization with and without the ligand present. These binding site adjustments are critical for flexible docking of new ligands to known structures or for docking to GPCR homology models. The ICM docking method has the potential to be used to "de-orphanize" orphan GPCRs (oGPCRs) and to identify antagonists-agonists for GPCRs if an accurate model (experimentally and computationally validated) of the structure has been constructed or when future crystal structures are determined.
- Published
- 2003
17. Analyses of circular dichroism spectra of membrane proteins
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Robert W. Janes, Andrew Orry, A. Lobley, Bonnie A. Wallace, and Jonathan G. Lees
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Circular dichroism ,Chemistry ,Circular Dichroism ,Analytical chemistry ,Membrane Proteins ,Dielectric ,Biochemistry ,Article ,Spectral line ,Wavelength ,Crystallography ,Membrane ,Membrane protein ,Animals ,Horses ,Spectroscopy ,Molecular Biology ,Protein secondary structure - Abstract
Circular dichroism (CD) spectroscopy is a valuable technique for the determination of protein secondary structures. Many linear and nonlinear algorithms have been developed for the empirical analysis of CD data, using reference databases derived from proteins of known structures. To date, the reference databases used by the various algorithms have all been derived from the spectra of soluble proteins. When applied to the analysis of soluble protein spectra, these methods generally produce calculated secondary structures that correspond well with crystallographic structures. In this study, however, it was shown that when applied to membrane protein spectra, the resulting calculations produce considerably poorer results. One source of this discrepancy may be the altered spectral peak positions (wavelength shifts) of membrane proteins due to the different dielectric of the membrane environment relative to that of water. These results have important consequences for studies that seek to use the existing soluble protein reference databases for the analyses of membrane proteins.
- Published
- 2003
18. Development of a highly selective allosteric antagonist radioligand for the type 1 cholecystokinin receptor and elucidation of its molecular basis of binding
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Ruben Abagyan, Maoqing Dong, David R. Haines, Laurence J. Miller, Arthur Christopoulos, Patrick M. Sexton, Ashton M. Vattelana, Polo C.-H. Lam, and Andrew Orry
- Subjects
Indoles ,Molecular model ,1.1 Normal biological development and functioning ,Allosteric regulation ,Drug design ,CHO Cells ,Biology ,Cholecystokinin receptor ,Radioligand Assay ,Cricetulus ,Underpinning research ,Chlorocebus aethiops ,Radioligand ,Cholecystokinin B ,Site-Directed ,Animals ,Humans ,Cholecystokinin A ,Pharmacology & Pharmacy ,Amino Acids ,Pharmacology ,Binding Sites ,Neurosciences ,Pharmacology and Pharmaceutical Sciences ,Articles ,Receptor, Cholecystokinin B ,Receptor, Cholecystokinin A ,Molecular Docking Simulation ,Transmembrane domain ,Biochemistry ,Docking (molecular) ,Mutagenesis ,COS Cells ,Biophysics ,Mutagenesis, Site-Directed ,Molecular Medicine ,Biochemistry and Cell Biology ,Receptor - Abstract
Understanding the molecular basis of ligand binding to receptors provides insights useful for rational drug design. This work describes development of a new antagonist radioligand of the type 1 cholecystokinin receptor (CCK1R), (2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-l-H-indole-3-propanoate (T-0632), and exploration of the molecular basis of its binding. This radioligand bound specifically with high affinity within an allosteric pocket of CCK1R. T-0632 fully inhibited binding and action of CCK at this receptor, while exhibiting no saturable binding to the closely related type 2 cholecystokinin receptor (CCK2R). Chimeric CCK1R/CCK2R constructs were used to explore the molecular basis of T-0632 binding. Exchanging exonic regions revealed the functional importance of CCK1R exon 3, extending from the bottom of transmembrane segment (TM) 3 to the top of TM5, including portions of the intramembranous pocket as well as the second extracellular loop region (ECL2). However, CCK1R mutants in which each residue facing the pocket was changed to that present in CCK2R had no negative impact on T-0632 binding. Extending the chimeric approach to ECL2 established the importance of its C-terminal region, and site-directed mutagenesis of each nonconserved residue in this region revealed the importance of Ser(208) at the top of TM5. A molecular model of T-0632-occupied CCK1R was consistent with these experimental determinants, also identifying Met(121) in TM3 and Arg(336) in TM6 as important. Although these residues are conserved in CCK2R, mutating them had a distinct impact on the two closely related receptors, suggesting differential orientation. This establishes the molecular basis of binding of a highly selective nonpeptidyl allosteric antagonist of CCK1R, illustrating differences in docking that extend beyond determinants attributable to distinct residues lining the intramembranous pocket in the two receptor subtypes.
- Published
- 2014
19. Modeling and Docking the Endothelin G-Protein-Coupled Receptor
- Author
-
Andrew Orry and Bonnie A. Wallace
- Subjects
Models, Molecular ,Rhodopsin ,Molecular Sequence Data ,Biophysics ,Drug design ,Ligands ,Protein Structure, Secondary ,GTP-Binding Proteins ,Animals ,Humans ,Amino Acid Sequence ,Binding site ,Nuclear Magnetic Resonance, Biomolecular ,G protein-coupled receptor ,Binding Sites ,biology ,Endothelin-1 ,Sequence Homology, Amino Acid ,Receptors, Endothelin ,Cell Membrane ,Receptor, Endothelin A ,Endothelin 1 ,Transmembrane protein ,Peptide Fragments ,Biochemistry ,Docking (molecular) ,biology.protein ,Cattle ,Sequence Alignment ,Alpha helix ,Algorithms ,Research Article - Abstract
A model of the endothelin G-protein-coupled receptor (ETA) has been constructed using a segmented approach. The model was produced using a bovine rhodopsin model as a template for the seven transmembrane α-helices. The three cytoplasmic loop regions and the C-terminal region were modeled on NMR structures of corresponding segments from bovine rhodopsin. The three extracellular loops were modeled on homologous loop regions in other proteins of known structure. The N-terminal region was modeled as a three-helix domain based on its homology with a hydrolase protein. To test the model, the FTDOCK algorithm was used to predict the ligand-binding site for the crystal structure of human endothelin. The site of docking is consistent with mutational and biochemical data. The principal sites of interaction in the endothelin ligand all lie on one face of a helix that has been implicated by structure-activity relationship studies as being essential for binding. As further support for the model, attempts to dock bigET, an inactive precursor to endothelin that does not bind to the receptor, found no sites for tight binding. The model of the receptor-ligand complex produced forms a basis for rational drug design of agonists and antagonists for this G-protein-coupled receptor.
- Published
- 2000
- Full Text
- View/download PDF
20. Probing the Role of E304 in the Allosteric Site of ADPGlucose Pyrophosphorylase from Agrobacterium tumefaciens
- Author
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Christopher R Meyer, Simona Bor, Andrew Orry, Hoomai Karzai, and Kevin Chastain
- Subjects
biology ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Allosteric regulation ,Genetics ,Agrobacterium tumefaciens ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2013
21. Structure‐Function Studies of the ADPGlucose Pyrophosphorylase from Thermodesulfovibrio yellowstonii
- Author
-
Sandeep Kaur, Matthew Badal, Christopher R Meyer, Andrew Orry, Michael Susoeff, Eric Yik, and Guatam Dua
- Subjects
Thermodesulfovibrio yellowstonii ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Structure function ,Genetics ,Molecular Biology ,Biotechnology - Published
- 2013
22. Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping
- Author
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Polo C.-H. Lam, Patrick M. Sexton, Joshua A. Makhoul, Andrew Orry, Xiequn Xu, Delia I. Pinon, Alicja M. Ball, Ruben Abagyan, Maoqing Dong, and Laurence J. Miller
- Subjects
Models, Molecular ,Molecular model ,Proline ,Phenylalanine ,Plasma protein binding ,CHO Cells ,Biology ,Ligands ,Biochemistry ,Binding, Competitive ,Secretin ,Research Communications ,Receptors, G-Protein-Coupled ,Receptors, Gastrointestinal Hormone ,Cricetulus ,Cricetinae ,Chlorocebus aethiops ,Protein Interaction Mapping ,Genetics ,Extracellular ,Animals ,Humans ,Cysteine ,Disulfides ,Receptor ,Molecular Biology ,G protein-coupled receptor ,COS cells ,Tryptophan ,Protein Structure, Tertiary ,COS Cells ,Mutation ,Peptides ,Biotechnology ,Protein Binding - Abstract
While it is evident that the carboxyl-terminal region of natural peptide ligands bind to the amino-terminal domain of class B GPCRs, how their biologically critical amino-terminal regions dock to the receptor is unclear. We utilize cysteine trapping to systematically explore spatial approximations among residues in the first five positions of secretin and in every position within the receptor extracellular loops (ECLs). Only Cys2 and Cys5 secretin analogues exhibited full activity and retained moderate binding affinity (IC50: 92±4 and 83±1 nM, respectively). When these peptides probed 61 human secretin receptor cysteine-replacement mutants, a broad network of receptor residues could form disulfide bonds consistent with a dynamic ligand-receptor interface. Two distinct patterns of disulfide bond formation were observed: Cys2 predominantly labeled residues in the amino terminus of ECL2 and ECL3 (relative labeling intensity: Ser340, 94±7%; Pro341, 84±9%; Phe258, 73±5%; Trp274 62±8%), and Cys5 labeled those in the carboxyl terminus of ECL2 and ECL3 (Gln348, 100%; Ile347, 73±12%; Glu342, 59±10%; Phe351, 58±11%). These constraints were utilized in molecular modeling, providing improved understanding of the structure of the transmembrane bundle and interconnecting loops, the orientation between receptor domains, and the molecular basis of ligand docking. Key spatial approximations between peptide and receptor predicted by this model (H1-W274, D3-N268, G4-F258) were supported by mutagenesis and residue-residue complementation studies.—Dong, M., Xu, X., Ball, A. M., Makhoul, J. A., Lam, P. C.-H., Pinon, D. I., Orry, A., Sexton, P. M., Abagyan, R., Miller, L. J. Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping.
- Published
- 2012
23. Evidence for Specific Roles of Arginines 26 and 38 in the Allosteric Regulation of ADP Glucose Pyrophosphorylase from Thermus thermophilus
- Author
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Fabian Botero, Jamie Sanders, Dhaval Doshi, Andrew Orry, Christopher R Meyer, and Teddy Truc
- Subjects
biology ,Biochemistry ,Chemistry ,Allosteric regulation ,Genetics ,ADP Glucose ,Thermus thermophilus ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2012
24. Probing the Role of Proline‐288 in the Regulation of Agrobacterium tumefaciens ADPGlucose Pyrophosphorylase
- Author
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David Guzman, Gagandeep Bains, Jamie Sanders, Simona Bor, Christopher R Meyer, Andrew Orry, and Hoomai Karzai
- Subjects
biology ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Genetics ,Agrobacterium tumefaciens ,Proline ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2012
25. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor
- Author
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David J. Meyers, Cecilia A. Larocca, Glen Liszczak, Marc A. Holbert, Ronen Marmorstein, Philip A. Cole, Hua Yuan, Yan Sun, Chandrani Mukherjee, Rhoda M. Alani, Erin M. Bowers, Gai Yan, Louis C. Mahadevan, Catherine A. Hazzalin, S. Adrian Saldanha, Andrew Orry, Ruben Abagyan, Nicholas T. Crump, and Ling Wang
- Subjects
Lysine Acetyltransferases ,Clinical Biochemistry ,Antineoplastic Agents ,P300-CBP Transcription Factors ,Crystallography, X-Ray ,Ligands ,Benzoates ,Binding, Competitive ,Biochemistry ,Small Molecule Libraries ,Mice ,Structure-Activity Relationship ,Catalytic Domain ,Cell Line, Tumor ,Drug Discovery ,Animals ,Computer Simulation ,p300-CBP Transcription Factors ,Enzyme Inhibitors ,Pyrazolones ,Molecular Biology ,Histone Acetyltransferases ,Pharmacology ,Binding Sites ,biology ,Acetylation ,DNA ,General Medicine ,Histone acetyltransferase ,Small molecule ,CHEMBIO ,Histone ,biology.protein ,Pyrazoles ,Molecular Medicine ,CELLBIO - Abstract
SummaryThe histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a Ki of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.
- Published
- 2010
26. Probing the Active Site of Thermotoga Maritima ADPGlucose Pyrophosphorylase
- Author
-
Adrianna Arteaga, Christopher R Meyer, Mikiko Matsui, and Andrew Orry
- Subjects
biology ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Thermotoga maritima ,Genetics ,biology.protein ,Active site ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2010
27. Characterization of the Thermotoga maritima ADP‐glucose pyrophosphorylase: Both glgC and glgD Subunits are Required for Optimal Activity and Allosteric regulation
- Author
-
Mikiko Matsui, Erick Guandique, Margaret Tran, Christopher R Meyer, Sean Nisperos, and Andrew Orry
- Subjects
0303 health sciences ,biology ,Chemistry ,030302 biochemistry & molecular biology ,Allosteric regulation ,ADP Glucose ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,Thermotoga maritima ,Genetics ,Molecular Biology ,030304 developmental biology ,Biotechnology - Published
- 2010
28. Probing the Role of Aspartate‐378 in the Regulation of ADPGlucose Pyrophosphorylase from Rhodobacter sphaeroides
- Author
-
Mikiko Matsui, Andrew Orry, Christopher R Meyer, and Paola Fernandez
- Subjects
0303 health sciences ,biology ,Chemistry ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,Rhodobacter sphaeroides ,0302 clinical medicine ,ADPGlucose Pyrophosphorylase ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2009
29. Both Subunits of Thermotoga maritima ADPGlucose Pyrophosphorylase are Required for Optimal Acitvity and Allosteric Regulation
- Author
-
David Rafael Abreu Reyes, Christopher R Meyer, Margaret Tran, Andrew Orry, Tala Harake, Mikiko Matsui, Erick Guandique, and Shannon Lim
- Subjects
0303 health sciences ,biology ,Chemistry ,Allosteric regulation ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,ADPGlucose Pyrophosphorylase ,Thermotoga maritima ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2009
30. Identification and characterization of a novel p300 HAT inhibitor
- Author
-
Ling Wang, David J. Meyers, Erin M. Bowers, Philip A. Cole, Chandrani Mukherjee, Cecilia A. Larocca, Rhoda M. Alani, Andrew Orry, and Gai Yan
- Subjects
Computer science ,Genetics ,Identification (biology) ,Computational biology ,Molecular Biology ,Biochemistry ,Biotechnology ,Characterization (materials science) - Published
- 2009
31. Probing the Molecular Basis for Heat Stability and Substrate and Activator Specificity for Thermus thermophilus ADPGlucose Pyrophosphorylase
- Author
-
Shrey Bhatt, Nicul Harkison, Christopher R Meyer, Andrew Orry, Dhaval Doshi, and Mikiko Matsui
- Subjects
0303 health sciences ,biology ,Activator (genetics) ,Chemistry ,Substrate (chemistry) ,Heat stability ,Thermus thermophilus ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,ADPGlucose Pyrophosphorylase ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2009
32. Molecular Characterization of Thermus Thermophilus ADPGlucose Pyrophosphorylase
- Author
-
Jacob Gonzalez, Ruben Abagyan, Andrew Orry, Go Watanabe, and Christopher R Meyer
- Subjects
0303 health sciences ,biology ,Chemistry ,Thermus thermophilus ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,ADPGlucose Pyrophosphorylase ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2008
33. Characterization of Thermus thermophilus ADPGlucose Pyrophosphorylase
- Author
-
Jacob Gonzalez, Andrew Orry, Ruben Abagyan, Go Watanabe, and Christopher R Meyer
- Subjects
0303 health sciences ,biology ,Chemistry ,Thermus thermophilus ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,ADPGlucose Pyrophosphorylase ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2007
34. Probing the Activator Specificity of Rhodospirillum rubrum ADPGlucose Pyrophosphorylase
- Author
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Ruben Abagyan, Adeel Amer, Jared Wiig, Chintan Amin, Dhaval Doshi, Christopher R Meyer, Andrew Orry, and Piranid Charoensak
- Subjects
biology ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Rhodospirillum rubrum ,Activator (phosphor) ,Genetics ,biology.organism_classification ,Molecular Biology ,Biotechnology - Published
- 2007
35. Probing the Activator Specificity of ADP‐Glucose Pyrophosphorylase from Rhodospirillum rubrum
- Author
-
Matoya Robinson, Jared Wiig, Christopher R Meyer, Shivani Patel, Ruben Abagyan, Dhaval Doshi, and Andrew Orry
- Subjects
0303 health sciences ,biology ,Chemistry ,Rhodospirillum rubrum ,ADP Glucose ,biology.organism_classification ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Activator (phosphor) ,Genetics ,Molecular Biology ,030217 neurology & neurosurgery ,030304 developmental biology ,Biotechnology - Published
- 2006
36. Expression, Purification, and Initial Characterization of the Diverse ADPGlucose Pyrophosphorylase from Thermodesulfovibrio yellowstonii
- Author
-
Andrew Orry, Tyber Cheever, Christopher R Meyer, Tu Kieu, and Michael Berriman
- Subjects
Thermodesulfovibrio yellowstonii ,Biochemistry ,Chemistry ,ADPGlucose Pyrophosphorylase ,Genetics ,Molecular Biology ,Biotechnology
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