2023
Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase
Maschietto F, Morzan U, Tofoleanu F, Gheeraert A, Chaudhuri A, Kyro G, Nekrasov P, Brooks B, Loria J, Rivalta I, Batista V. Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase. Nature Communications 2023, 14: 2239. PMID: 37076500, PMCID: PMC10115891, DOI: 10.1038/s41467-023-37956-1.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAllosteric SiteAmino AcidsGlycerolImidazolesMolecular Dynamics SimulationPhosphatesConceptsEffector bindingImidazole Glycerol Phosphate SynthaseLocal amino acidsAmino acid dynamicsImidazole glycerolAllosteric drugsAllosteric activationAllosteric responsePhosphate synthaseAllosteric mechanismMode of activationEnzyme functionAmino acidsAllosteryDrug discoverySynthaseNuclear magnetic resonance spectroscopyBindingMolecular dynamics simulationsActivationAllostericCascadeDynamics simulations
2021
Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9
Nierzwicki L, East K, Morzan U, Arantes P, Batista V, Lisi G, Palermo G. Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9. ELife 2021, 10: e73601. PMID: 34908530, PMCID: PMC8741213, DOI: 10.7554/elife.73601.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationCRISPR-Cas SystemsGenetic VariationGenotypeMolecular Dynamics SimulationMolecular StructureMutationStreptococcus pyogenesConceptsHNH domainAllosteric communicationCatalytic HNH domainDNA recognition regionSpecificity-enhancing mutationsGenome editing capabilitiesAllosteric signalingAllosteric signalMutations perturbAllosteric hotspotsSpecificity enhancementCas9 endonucleaseMutational studiesDNA recognitionAllosteric connectivityAllosteric roleMolecular toolsAllosteric structureRecognition regionMolecular levelBiochemical studiesDNA cleavageSolution NMRMutationsCatalytic site
2020
Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase
Beaumont VA, Reiss K, Qu Z, Allen B, Batista VS, Loria JP. Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase. Biochemistry 2020, 59: 1896-1908. PMID: 32348128, PMCID: PMC7364816, DOI: 10.1021/acs.biochem.0c00245.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationBiocatalysisDual Specificity Phosphatase 3HumansHydrolysisKineticsModels, MolecularMutagenesis, Site-DirectedProtein ConformationConceptsAcid loopVariable insertActive siteActive-site hydrogen bondsInsert regionSolution nuclear magnetic resonanceNuclear magnetic resonanceMillisecond motionsActive site environmentNormal catalytic functionActive site altersMolecular dynamics simulationsActive site loopHydrogen bondsVaccinia H1Asparagine 74Protein tyrosineTyrosine phosphataseRapid kinetic measurementsAllosteric regionActivity of enzymesKinetic measurementsDynamics simulationsConformational motionsInsert loop
2012
Allosteric pathways in imidazole glycerol phosphate synthase
Rivalta I, Sultan MM, Lee NS, Manley GA, Loria JP, Batista VS. Allosteric pathways in imidazole glycerol phosphate synthase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: e1428-e1436. PMID: 22586084, PMCID: PMC3365145, DOI: 10.1073/pnas.1120536109.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAllosteric RegulationAllosteric SiteAminohydrolasesBacterial ProteinsBinding SitesBiocatalysisCrystallography, X-RayImidazolesKineticsModels, MolecularMolecular Dynamics SimulationProtein BindingProtein ConformationProtein MultimerizationProtein Structure, TertiaryProtein SubunitsRibonucleotidesSignal TransductionThermotoga maritimaConceptsAllosteric pathwayImidazole glycerolNucleotide biosynthetic pathwayGlutaminase active siteProtein-protein interfacesGlutamine-binding siteNew allosteric drugsImportant branch pointSolution NMR techniquesAllosteric drugsBiosynthetic pathwayAllosteric mechanismCommunity analysisCorrelated protein motionsInactive enzymeProtein motionsPRFARAlternative herbicidesPotential therapeutic targetPathwayTherapeutic targetActive siteNMR techniquesBranch pointsFundamental insights