11 results on '"AMP binding"'
Search Results
2. Structure and function of AMP-activated protein kinase
- Author
-
Bruce E. Kemp, Jonathan S. Oakhill, and John W. Scott
- Subjects
Models, Molecular ,Binding Sites ,Molecular Structure ,Protein Conformation ,Physiology ,Protein subunit ,Molecular Sequence Data ,AMPK ,AMP binding ,AMP-Activated Protein Kinases ,Biology ,Adenosine Monophosphate ,Cell biology ,Enzyme Activation ,Protein Subunits ,Enzyme activator ,Protein structure ,AMP-activated protein kinase ,biology.protein ,Animals ,Amino Acid Sequence ,Protein kinase A ,Signal Transduction ,Gamma subunit - Abstract
AMP-activated protein kinase (AMPK) regulates metabolism in response to energy demand and supply. AMPK is activated in response to rises in intracellular AMP or calcium-mediated signalling and is responsible for phosphorylating a wide variety of substrates. Recent structural studies have revealed the architecture of the alphabetagamma subunit interactions as well as the AMP binding pockets on the gamma subunit. The alpha catalytic domain (1-280) is autoinhibited by a C-terminal tail (313-335), which is proposed to interact with the small lobe of the catalytic domain by homology modelling with the MARK2 protein structure. Two direct activating drugs have been reported for AMPK, the thienopyridone compound A769662 and PTI, which may activate by distinct mechanisms.
- Published
- 2009
3. The antimicrobial peptide-sensing system aps of Staphylococcus aureus
- Author
-
Michael Otto, David J. Cha, Min Li, Daniel E. Sturdevant, Amer E. Villaruz, and Yuping Lai
- Subjects
Staphylococcus aureus ,Antimicrobial peptides ,Virulence ,Human pathogen ,Peptide ,AMP binding ,Biology ,medicine.disease_cause ,Sensitivity and Specificity ,Microbiology ,Mice ,chemistry.chemical_compound ,Drug Resistance, Bacterial ,Staphylococcus epidermidis ,medicine ,Animals ,Humans ,Molecular Biology ,chemistry.chemical_classification ,Teichoic acid ,Lysine ,Cell Membrane ,Gene Expression Regulation, Bacterial ,Staphylococcal Infections ,AMP transport ,Community-Acquired Infections ,Teichoic Acids ,chemistry ,Female ,Methicillin Resistance ,Carrier Proteins ,Antimicrobial Cationic Peptides - Abstract
Summary Staphylococcus aureus is a leading cause of hospital-associated and, more recently, community-associated infections caused by highly virulent methicillin-resistant strains (CA-MRSA). S. aureus survival in the human host is largely defined by the ability to evade attacks by antimicrobial peptides (AMPs) and other mechanisms of innate host defence. Here we show that AMPs induce resistance mechanisms in CA-MRSA via the aps AMP sensor/regulator system, including (i) the d-alanylation of teichoic acids, (ii) the incorporation of lysyl-phosphatidylglycerol in the bacterial membrane and a concomitant increase in lysine biosynthesis, and (iii) putative AMP transport systems such as the vraFG transporter, for which we demonstrate a function in AMP resistance. In contrast to the aps system of S. epidermidis, induction of the aps response in S. aureus was AMP-selective due to structural differences in the AMP binding loop of the ApsS sensor protein. Finally, using a murine infection model, we demonstrate the importance of the aps regulatory system in S. aureus infection. This study shows that while significant interspecies differences exist in the AMP–aps interaction, the AMP sensor system aps is functional and efficient in promoting resistance to a variety of AMPs in a clinically relevant strain of the important human pathogen S. aureus.
- Published
- 2007
4. Intrasteric control of AMPK via the 1 subunit AMP allosteric regulatory site
- Author
-
Michael W. Parker, Bruce E. Kemp, David Stapleton, Zhi-Ping Chen, Craig J. Morton, Lee A. Witters, Julian J. Adams, and Bryce J. W. van Denderen
- Subjects
Models, Molecular ,Molecular Sequence Data ,Allosteric regulation ,Glycine ,CBS domain ,Regulatory site ,AMP binding ,Biology ,Biochemistry ,Article ,Adenosine Triphosphate ,AMP-Activated Protein Kinase Kinases ,Chlorocebus aethiops ,Animals ,Point Mutation ,Amino Acid Sequence ,Phosphorylation ,Protein kinase A ,Molecular Biology ,Conserved Sequence ,G alpha subunit ,Binding Sites ,Sequence Homology, Amino Acid ,AMPK ,Hydrogen Bonding ,Adenosine Monophosphate ,Protein Structure, Tertiary ,Enzyme Activation ,Protein Subunits ,Amino Acid Substitution ,COS Cells ,Mutagenesis, Site-Directed ,Protein Kinases ,Allosteric Site ,Protein Binding ,Gamma subunit - Abstract
AMP-activated protein kinase (AMPK) is a alphabetagamma heterotrimer that is activated in response to both hormones and intracellular metabolic stress signals. AMPK is regulated by phosphorylation on the alpha subunit and by AMP allosteric control previously thought to be mediated by both alpha and gamma subunits. Here we present evidence that adjacent gamma subunit pairs of CBS repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site related to, but distinct from the classical AMP binding site in phosphorylase, that can also bind ATP. The AMP binding site of the gamma(1) CBS1/CBS2 pair, modeled on the structures of the CBS sequences present in the inosine monophosphate dehydrogenase crystal structure, contains three arginine residues 70, 152, and 171 and His151. The yeast gamma homolog, snf4 contains a His151Gly substitution, and when this is introduced into gamma(1), AMP allosteric control is substantially lost and explains why the yeast snf1p/snf4p complex is insensitive to AMP. Arg70 in gamma(1) corresponds to the site of mutation in human gamma(2) and pig gamma(3) genes previously identified to cause an unusual cardiac phenotype and glycogen storage disease, respectively. Mutation of any of AMP binding site Arg residues to Gln substantially abolishes AMP allosteric control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the previously described inhibitory properties of ATP and render the enzyme constitutively active. We propose that ATP acts as an intrasteric inhibitor by bridging the alpha and gamma subunits and that AMP functions to derepress AMPK activity.
- Published
- 2004
5. Conserved amino acids near the carboxy terminus of bacterial tyrosyl-tRNA synthetase are involved in tRNA and Tyr-AMP binding
- Author
-
Juan C. Salazar, Omar Orellana, Dieter Söll, Claudia Lefimil, and Roberto Zúñiga
- Subjects
Overexpression ,Biophysics ,Gene Expression ,AMP binding ,Biology ,Biochemistry ,Geobacillus stearothermophilus ,Structure-Activity Relationship ,Residue (chemistry) ,Bacterial Proteins ,RNA, Transfer ,Tyrosine-tRNA Ligase ,Structural Biology ,Escherichia coli ,Genetics ,Cloning, Molecular ,Molecular Biology ,Conserved Sequence ,chemistry.chemical_classification ,Sequence Homology, Amino Acid ,Genetic Complementation Test ,Mutagenesis ,Active site ,Cell Biology ,TRNA binding ,Adenosine Monophosphate ,Amino acid ,Enzyme ,chemistry ,tRNA binding domain ,Transfer RNA ,Mutagenesis, Site-Directed ,biology.protein ,Tyrosine ,Dimerization ,Fusion protein ,Gammaproteobacteria - Abstract
Bacterial tyrosyl-tRNA synthetases occur in two large subfamilies, TyrRS and TyrRZ, that possess about 25% amino acid identity. Their amino-terminal region, the active site domain, is more conserved (>36% identity). The carboxy-terminal segment of these enzymes includes the tRNA binding domain and contains only few conserved residues. Replacement of three of these residues in Acidithiobacillus ferrooxidans TyrRZ revealed that S356 and K395 play roles in tRNA binding, while H306, a residue at the junction of the catalytic and tRNA binding domains, stabilizes the Tyr-AMP:TyrRZ complex. The replacement data suggest that conserved amino acids in A. ferrooxidans TyrRZ and Bacillus stearothermophilus TyrRS play equivalent roles in enzyme function.
- Published
- 2001
6. When fold is not important: A common structural framework for adenine and AMP binding in 12 unrelated protein families
- Author
-
Mark S. Johnson and Konstantin Denessiouk
- Subjects
chemistry.chemical_classification ,DNA ligase ,Protein family ,AMP binding ,Tripeptide ,computer.file_format ,Biology ,Protein Data Bank ,Biochemistry ,chemistry ,Structural Biology ,Moiety ,Binding site ,Protein kinase A ,Molecular Biology ,computer - Abstract
ATP is a ligand common to many proteins, yet it is unclear whether common recognition patterns do exist among the many different folds that bind ATP. Previously, it was shown that cAMP-dependent protein kinase, D-Ala:D-Ala ligase and the α-subunit of the α2β2 ribonucleotide reductase do share extensive common structural elements for ATP recognition although their folds are different. Here, we have made a survey of structures that bind ATP and compared them with the key features seen in these three proteins. Our survey shows that 12 different fold types share a specific recognition pattern for the adenine moiety, and 8 of these folds have a common structural framework for recognition of the AMP moiety of the ligand. The common framework consists of a tripeptide segment plus three additional residues, which provides similar polar and hydrophobic interactions between the protein and mononucleotide. Consensus interactions are represented by four key hydrogen bonds present in each fold type. Two of these four hydrogen bonds, together with three aliphatic residues, form a specific recognition pattern for the adenine moiety in all 12 folds. These similarities point to a structural-functional requirement shared by these different mononucleotide-binding proteins that represent at this time 28% of the adenine mononucleotide complexes found in the Brookhaven Protein Data Bank. Proteins 2000;38:310–326. © 2000 Wiley-Liss, Inc.
- Published
- 2000
7. Towards a mechanism of AMP-substrate inhibition in adenylate kinase fromEscherichia coli
- Author
-
Varda Ittah, Elisha Haas, Elena V. Sineva, and Michael A. Sinev
- Subjects
Biophysics ,Adenylate kinase ,AMP binding ,Substrate inhibition ,Ligands ,medicine.disease_cause ,Biochemistry ,Adenosine Triphosphate ,Structural Biology ,Escherichia coli ,Genetics ,medicine ,Site-directed mutagenesis ,Molecular Biology ,chemistry.chemical_classification ,Binding Sites ,Adenylate Kinase ,Substrate (chemistry) ,Time-resolved fluorescence ,Cell Biology ,Probe ,Adenosine Monophosphate ,Spectrometry, Fluorescence ,Förster resonance energy transfer ,Enzyme ,Energy Transfer ,chemistry ,Mutagenesis, Site-Directed ,Cysteine - Abstract
Crystallographic studies on adenylate kinase (AK) suggest that binding of ATP causes the LID domain of the enzyme to close over the ATP molecule (Schlauderer et al. (1996) J. Mol. Biol. 256, 223-227). The method of time-resolved fluorescence resonance energy transfer was applied to study the proposed structural change in AK from Escherichia coli. Two active derivatives of the (C77S, A73C, V142C)-AK mutant containing the excitation energy donor attached to one of the two cysteine residues and the acceptor attached to the other cysteine were prepared to monitor displacements of the LID domain in response to substrate binding. Binding of either ATP or AMP was accompanied by an approximately 9 A decrease in the interprobe distances suggesting LID domain closure. Closure of the LID domain in response to AMP binding may be a possible reason for the strong AMP-substrate inhibition known for E. coli AK.
- Published
- 1996
8. Mitochondrial GTP-AMP Phosphotransferase. 1. Purification and Properties
- Author
-
R. Heiner Schirmer, Alfredo G. Tomasselli, and Lafayette H. Noda
- Subjects
chemistry.chemical_classification ,GTP' ,Stereochemistry ,Phosphotransferases ,Substrate (chemistry) ,Guanosine ,AMP binding ,Biochemistry ,Adenosine Monophosphate ,Mitochondria, Heart ,Molecular Weight ,Phosphotransferase ,Dissociation constant ,chemistry.chemical_compound ,chemistry ,Animals ,Cattle ,Nucleotide ,Guanosine Triphosphate ,Amino Acids ,Binding site ,Nucleoside-Phosphate Kinase - Abstract
Kinetic and equilibrium dialysis substrate binding studies have been done to investigate the properties of mitochondrial GTP-AMP phosphotransferase. The results show that the enzyme has a specific requirement for divalent metal ions, namely Mg2+, Mn2+ or Ca2+ (Ca2+ is active only in the forward direction, the direction of formation of ADP). The reaction rate depends upon the ratio [Mg2+]: [substrate] rather than on the metal ion concentration alone. The enzymatic activity is influenced by NaCl (or KCl) and optimum pH occurs at 11.5 and 9.5 for guanosine and inosine nucleotides respectively. Examination of binding of substrates to the enzyme showed that there is one binding site (GTP site) for MgGTP, GTP, MgGDP or GDP per molecule of enzyme, with dissociation constants of 4.5, 4.4, 3.0, 2.2 μM respectively and one binding site (AMP site) for AMP, ADP or ATP per molecule of enzyme with dissociation constants of 20.9, 33.4 and 33.4 μM respectively. Since, within the limitations of equilibrium dialysis used in the present studies, AMP binding to one site of the enzyme could be detected only when GDP or GTP is present, the mechanism of the forward reaction may be assumed to be nearly ordered. For the reverse reaction there is no requirement of order of binding of the two nucleotides and so the mechanism of reaction may be assumed to be random.
- Published
- 1979
9. Mitochondrial GTP-AMP Phosphotransferase.. 2. Kinetic and Equilibrium Dialysis Studies
- Author
-
Lafayette H. Noda and Alfredo G. Tomasselli
- Subjects
chemistry.chemical_classification ,GTP' ,Cations, Divalent ,Osmolar Concentration ,Phosphotransferases ,Substrate (chemistry) ,Guanosine ,AMP binding ,Biochemistry ,Adenosine Monophosphate ,Mitochondria, Heart ,Substrate Specificity ,Dissociation constant ,Phosphotransferase ,Kinetics ,chemistry.chemical_compound ,chemistry ,Biophysics ,Animals ,Cattle ,Nucleotide ,Guanosine Triphosphate ,Binding site ,Nucleoside-Phosphate Kinase ,Dialysis - Abstract
Kinetic and equilibrium dialysis substrate binding studies have been done to investigate the properties of mitochondrial GTP-AMP phosphotransferase. The results show that the enzyme has a specific requirement for divalent metal ions, namely Mg2+, Mn2+ or Ca2+ (Ca2+ is active only in the forward direction, the direction of formation of ADP). The reaction rate depends upon the ratio [Mg2+]:[substrate] rather than on the metal ion concentration alone. The enzymatic activity is influenced by NaCl (or KCl) and optimum pH occurs at 11.5 and 9.5 for guanosine and inosine nucleotides respectively. Examination of binding of substrates to the enzyme showed that there is one binding site (GTP site) for MgGTP, GTP, MgGDP or GDP per molecule of enzyme, with dissociation constants of 4.5, 4.4, 3.0, 2.2 micron respectively and one binding site (AMP site) for AMP, ADP or ATP per molecule of enzyme with dissociation constants of 20.9, 33.4 and 33.4 microns respectively. Since, within the limitations of equilibrium dialysis used in the present studies, AMP binding to one site of the enzyme could be detected only when GDP or GTP is present, the mechanism of the forward reaction may be assumed to be nearly ordered. For the reverse reaction there is no requirement of order of binding of the two nucleotides and so the mechanism of reaction may be assumed to be random.
- Published
- 1979
10. Dinitrophenylation of a single cysteine side chain in phosphorylasebfrom rabbit muscle with concomitant blocking of AMP binding
- Author
-
H.G. Bäumert, F. Ortanderl, F. Keller, M. Halbach, and H. Fasold
- Subjects
Electrophoresis ,Phosphorylases ,Stereochemistry ,Biophysics ,AMP binding ,In Vitro Techniques ,Biochemistry ,chemistry.chemical_compound ,Glycogen phosphorylase ,Dinitrofluorobenzene ,Structural Biology ,Genetics ,Animals ,Cysteine ,Pyridoxal phosphate ,Molecular Biology ,Nitrobenzenes ,chemistry.chemical_classification ,Carbon Isotopes ,Binding Sites ,Muscles ,Proteins ,Fluorine ,Cell Biology ,Adenosine Monophosphate ,Enzyme ,chemistry ,Thiolysis ,Dinitrophenyl ,Rabbits ,Peptides ,Ultracentrifugation ,Dinitrophenols ,Protein Binding - Abstract
The inactivation of rabbit muscle phosphorylase b by dinitrofluorobenzene (DNFB) at pH 7.5-8.0 was investigated by several groups [l-4] . One sulfhydryl, which seems to be covered up by pyridoxal phosphate in the native enzyme, could be identified by this method in apo-phosphorylase, and the sequence of a peptic peptide around this cysteine was determined [ 11. At least one SH group was found to be implicated in AMP binding of the b form of the enzyme, however, a clear decision between at least two corresponding peptic sequences could not be made [2,3, 51. As reported in a preliminary communication [4], we have found that the inactivation of phosphorylase b by DNFB proceeds more slowly and more specifically at pH 6.0-6.5. A subsequent thiolysis by mercaptoethanol [6] removes all dinitrophenyl groups except one from the modified enzyme.
- Published
- 1973
11. Activation of AMP-binding Sites
- Author
-
Robert A. Steinberg, Joanne L. Russell, David A. Yphantis, and Caroline S. Murphy
- Subjects
History and Philosophy of Science ,Biochemistry ,Chemistry ,General Neuroscience ,AMP binding ,General Biochemistry, Genetics and Molecular Biology - Published
- 1986
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.