Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin
Cramer J, Krimmer S, Fridh V, Wulsdorf T, Karlsson R, Heine A, Klebe G. Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin. ACS Chemical Biology 2016, 12: 225-233. PMID: 27959500, DOI: 10.1021/acschembio.6b00979.Peer-Reviewed Original ResearchMeSH KeywordsAspartic AcidCrystallography, X-RayDipeptidesEnzyme InhibitorsHydrogen BondingKineticsModels, ChemicalMolecular ConformationOrganophosphorus CompoundsThermolysinTime FactorsConceptsCharge-assisted hydrogen bondsMetalloprotease thermolysinSurface plasmon resonance spectroscopyDrug discoveryHigh-resolution crystal structuresPlasmon resonance spectroscopyKinetic dataProtein-ligand interactionsStructure-kinetic relationshipsRational drug discoveryHigh conservationHydrogen bondsDissociation rate constantsStrength of interactionThermolysin inhibitorsMetalloprotease familyCrystal structureMolecular mechanismsSide chainsStrand motifResonance spectroscopyStructural motifsRate constantsRate-limiting stepLigand release