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40 results on '"Suardíaz, Reynier"'

3. Unveiling Novel Urease Inhibitors for Helicobacter pylori: A Multi-Methodological Approach from Virtual Screening and ADME to Molecular Dynamics Simulations

Author

Valenzuela-Hormazabal, Paulina, primary, Sepúlveda, Romina V., additional, Alegría-Arcos, Melissa, additional, Valdés-Muñoz, Elizabeth, additional, Rojas-Pérez, Víctor, additional, González-Bonet, Ileana, additional, Suardíaz, Reynier, additional, Galarza, Christian, additional, Morales, Natalia, additional, Leddermann, Verónica, additional, Castro, Ricardo I., additional, Benso, Bruna, additional, Urra, Gabriela, additional, Hernández-Rodríguez, Erix W., additional, and Bustos, Daniel, additional

Published
2024
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15. Resistance to the “last resort” antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes

Author

Lythell, Emily, primary, Suardíaz, Reynier, additional, Hinchliffe, Philip, additional, Hanpaibool, Chonnikan, additional, Visitsatthawong, Surawit, additional, Oliveira, A. Sofia F., additional, Lang, Eric J. M., additional, Surawatanawong, Panida, additional, Lee, Vannajan Sanghiran, additional, Rungrotmongkol, Thanyada, additional, Fey, Natalie, additional, Spencer, James, additional, and Mulholland, Adrian J., additional

Published
2020
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16. Understanding the molecular mechanism of the Ala-versus-Gly concept controlling the product specificity in reactions catalyzed by Lipoxygenases:a combined molecular dynamics and QM/MM study of coral 8R-Lipoxygenase

Author

Saura Martínez, Patricia, Suardíaz, Reynier, Masgrau, Laura, González-Lafont, Àngels, Rosta, Edina, and Lluch López, Josep Maria

Subjects
EPSRC, Ala-versus-Gly concept, arachidonic acid, free energy calculations, RCUK, molecular dynamics simulations, QM/MM calculations, coral 8R-lipoxygenase, EP/N020669/1, enzyme catalysis, Catalysis
Abstract

Lipoxygenases (LOXs) are a family of enzymes that catalyze the highly specific hydroperoxidation of polyunsaturated fatty acids, such as arachidonic acid. Different stereo- or/and regioisomer hydroperoxidation products lead later to different metabolites that exert opposite physiological effects in the animal body and play a central role in inflammatory processes. The Gly-Ala switch of a single residue is crucial for the stereo- and regiocontrol in many lipoxygenases. Herein, we have combined molecular dynamics simulations with quantum mechanics/molecular mechanics calculations to study the hydrogen abstraction step and the molecular oxygen addition step of the hydroperoxidation reaction of arachidonic acid catalyzed by both wild-type Coral 8R-LOX and its Gly427Ala mutant. We have obtained a detailed molecular understanding of this Ala-versus-Gly concept. In wild type, molecular oxygen adds to C8 of arachidonic acid with an R stereochemistry. In the mutant, Ala427 pushes Leu385, blocks the region over C8, and opens an oxygen access channel now directed to C12, where molecular oxygen is added with an S stereochemistry. Thus, the specificity turns out to be dramatically inverted. Since Leu385 is highly conserved among many lipoxygenase isoforms, this mechanism can be general, and we propose that the presence of such type of bulky and hydrophobic residues can be key in controlling the extreme regio- and stereospecificity of lipoxygenases and, as a consequence, their physiological effects.

Published
2017
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18. Structural Characterization of Arginine Fingers: Identification of an Arginine Finger for the Pyrophosphatase dUTPases

Author

Nagy, Gergely N., Suardíaz, Reynier, Lopata, Anna, Ozohanics, Olivér, Vékey, Károly, Brooks, Bernard R., Leveles, Ibolya, Tóth, Judit, Vértessy, Beata G., and Rosta, Edina

Abstract

Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the γ-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases.Arginine finger is a highly conserved and essential residue in many GTPase and AAA+ ATPase enzymes that completes the active site from a distinct protomer, forming contacts with the γ-phosphate of the nucleotide. To date, no pyrophosphatase has been identified that employs an arginine finger fulfilling all of the above properties; all essential arginine fingers are used to catalyze the cleavage of the γ-phosphate. Here, we identify and unveil the role of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arginine fingers. We found that the conserved arginine adjacent to the P-loop-like motif enables structural organization of the active site for efficient catalysis via its nucleotide coordination, while its direct electrostatic role in transition state stabilization is secondary. An exhaustive structure-based comparison of analogous, conserved arginines from nucleotide hydrolases and transferases revealed a consensus amino acid location and orientation for contacting the γ-phosphate of the substrate nucleotide. Despite the structurally equivalent position, functional differences between arginine fingers of dUTPases and NTPases are explained on the basis of the unique chemistry performed by the pyrophosphatase dUTPases.

Published
2016
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19. Biocatalytic Routes to Lactone Monomers for Polymer Production

Author

Messiha, Hanan L., primary, Ahmed, Syed T., additional, Karuppiah, Vijaykumar, additional, Suardíaz, Reynier, additional, Ascue Avalos, Gabriel A., additional, Fey, Natalie, additional, Yeates, Stephen, additional, Toogood, Helen S., additional, Mulholland, Adrian J., additional, and Scrutton, Nigel S., additional

Published
2018
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24. Quantum Mechanics/Molecular Mechanics Simulations Show Saccharide Distortion is Required for Reaction in Hen Egg‐White Lysozyme.

Author

Limb, Michael A. L., Suardíaz, Reynier, Grant, Ian M., and Mulholland, Adrian J.

Subjects
*QUANTUM mechanics/molecular mechanics, *LYSOZYMES, *SACCHARIDES, *CATALYSIS, *CONFORMATIONAL analysis
Abstract

Hybrid quantum mechanics/molecular mechanics (QM/MM) calculations on lysozyme show significant distortion of the bound saccharide is required to facilitate the catalytic reaction. QM/MM calculations on lysozyme show significant distortion of the bound saccharide is required to facilitate the catalytic reaction. The image shows the 2D PES from undistorted (left) and distorted (right) intermediate. The results indicate that reaction occurs via anti attack of Asp52, with subsequent conformational change. [ABSTRACT FROM AUTHOR]

Published
2019
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39. An Insight into the Regiospecificity of Linoleic AcidPeroxidation Catalyzed by Mammalian 15-Lipoxygenases.

Author

Suardíaz, Reynier, Masgrau, Laura, Lluch, JoséM., and González-Lafont, Àngels

Subjects
*LINOLEIC acid, *PEROXIDATION, *CATALYSIS, *LIPOXYGENASES, *MAMMALS, *QUANTUM mechanics, *NUMERICAL calculations
Abstract

15-Lipoxygenases(15-LOs) catalyze the peroxidation reaction oflinoleic acid (LA) in mammals producing almost exclusively 13-(S)-hydroperoxyoctadecadienoic acid (13-(S)-HPODE). Although several hypotheses have been formulated, the molecularbasis of such enzymatic regiospecificity is unclear. We have herecombined quantum mechanics/molecular mechanics (QM/MM) calculationswith molecular dynamics simulations to analyze the peroxidation mechanismusing a complete rabbit 15-LO-1/LA solvated model. C9andC13being equivalent for planarity and spin density, theQM/MM potential energy profiles of the O2addition to thosetwo atoms were calculated. The difference in the potential energybarrier heights is clear enough to justify that O2selectivelyattacks C13giving 13-(S)-HPODE. Oxygenationat C9is hindered by two steric-shielding residues (Leu597and Gln548). The calculated free energy profile at 300 K for the O2addition to C13confirms that the peroxidationon C13is a reversible viable process in agreement withexperiments. Thus, the subsequent reduction of the peroxyl radicalto give the final hydroperoxidated product is expected to give theirreversibility character to the overall process. [ABSTRACT FROM AUTHOR]

Published
2013
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40. On the unusual 2J(C2-H(f)) coupling dependence on syn/anti CHO conformation in 5-X-furan-2-carboxaldehydes.

Author

Pérez C, Suardíaz R, Ortiz PJ, Crespo-Otero R, Bonetto GM, Gavín JA, García de la Vega JM, San Fabián J, and Contreras RH

Subjects
Electrons, Models, Chemical, Molecular Conformation, Quantum Theory, Reference Standards, Stereoisomerism, Aldehydes chemistry, Furans chemistry, Magnetic Resonance Spectroscopy methods, Magnetic Resonance Spectroscopy standards
Abstract

A remarkable difference for (2)J(C(2)-H(f)) coupling constant in syn and anti conformers of 5-X-furan-2-carboxaldehydes (X = CH(3), Ph, NO(2), Br) and a rationalization of this difference are reported. On the basis of the current knowledge of the Fermi-contact term transmission, a rather unusual dual-coupling pathway in the syn conformer is presented. The additional coupling pathway resembles somewhat that of the J(H-H) in homoallylic couplings, which are transmitted by hyperconjugative interactions involving the pi(C=C) electronic system. The homoallylic coupling pathway can be labeled as sigma*(C-H) <-- pi(C=C) --> sigma*(C-H). In the present case, this additional coupling pathway, using an analogous notation, can be labeled as sigma*(C(2)-C(C)) <-- LP(1)(O(1))...LP(2)(O(C)) --> sigma*(C(C)-H(f)) (sigma*(C(2)-C(C))) where O(1) and O(C) stand for the ring and carbonyl O atoms, respectively. This additional coupling pathway is not activated in the anti conformers since both oxygen lone pairs do not overlap., (2008 John Wiley & Sons, Ltd.)

Published
2008
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