0000000000952936

AUTHOR

Julio Caballero

showing 4 related works from this author

Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: a QM/MM study

2019

AbstractCyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and protein kinases in general, a detailed understanding of the reaction mechanism is desired. Thus, in this work the phosphoryl transfer reaction catalyzed by CDK2 was revisited and studied by means of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Our results show that the base-assisted mechanism is preferred over the substrat…

Models MolecularComposite ParticlesProtein ConformationPhysical ChemistryBiochemistry01 natural sciencesSubstrate Specificitychemistry.chemical_compoundPhosphorylationPost-Translational ModificationFree Energy0303 health sciencesMultidisciplinarybiologyKinasePhysicsQChemical ReactionsRChemistryReaction DynamicsPhysical SciencesThermodynamicsMedicineProtonsResearch ArticleChemical ElementsAtomsStereochemistryScienceMolecular Dynamics Simulation010402 general chemistryMolecular mechanicsReactantsQM/MMStructure-Activity Relationship03 medical and health sciencesCyclin-dependent kinaseParticle PhysicsNuclear PhysicsNucleons030304 developmental biologyChemical BondingCyclin-Dependent Kinase 2Cyclin-dependent kinase 2Biology and Life SciencesProteinsActive siteHydrogen BondingTransition StateBond order0104 chemical sciencesOxygenModels Chemicalchemistrybiology.proteinQuantum TheoryAdenosine triphosphate
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Studying the phosphoryl transfer mechanism of the E. coli phosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simula…

2019

Phosphofructokinases (Pfks) catalyze the ATP-dependent phosphorylation of fructose-6-phosphate (F6P) and they are regulated in a wide variety of organisms. Although numerous aspects of the kinetics and regulation have been characterized for Pfks, the knowledge about the mechanism of the phosphoryl transfer reaction and the transition state lags behind. In this work, we describe the X-ray crystal structure of the homodimeric Pfk-2 from E. coli, which contains products in one site and reactants in the other, as well as an additional ATP molecule in the inhibitory allosteric site adjacent to the reactants. This complex was previously predicted when studying the kinetic mechanism of ATP inhibit…

Reaction mechanism010405 organic chemistryChemistryMetaphosphateKineticsAllosteric regulationGeneral Chemistry010402 general chemistry01 natural sciencesMolecular mechanics0104 chemical sciencesMolecular dynamicschemistry.chemical_compoundBACTÉRIAS GRAM-NEGATIVASQuantum mechanicsMoleculePhosphofructokinasesChemical Science
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On the Nature of the Enzyme–Substrate Complex and the Reaction Mechanism in Human Arginase I. A Combined Molecular Dynamics and QM/MM Study

2020

We present here a detailed theoretical analysis of L-arginine hydrolysis catalyzed by Human Arginase I (HARGI). Our study combines classical molecular dynamic simulations of different model for the...

chemistry.chemical_classificationReaction mechanism010405 organic chemistryChemistrySubstrate (chemistry)General Chemistry010402 general chemistry01 natural sciencesCombinatorial chemistryCatalysis0104 chemical sciencesCatalysisArginaseQM/MMMolecular dynamicsHydrolysisEnzymeACS Catalysis
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Studying the phosphoryl transfer mechanism of the

2019

Phosphofructokinases catalyze the ATP-dependent phosphorylation of fructose-6-phosphate and they are highly regulated.

inorganic chemicalsenzymes and coenzymes (carbohydrates)Chemistrybacteriamacromolecular substancesenvironment and public healthChemical science
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