title: Enzyme isoselective inhibitors: a tool for binding-trend analysis.
abstract: A transition-state analogue inhibitor that covalently reversibly binds to an enzyme formally consists of two parts: the chemical site, CS and the recognition site, RS. We have experimentally and theoretically demonstrated that the trend of binding affinity in a series of isoselective inhibitors (with identical RS and different CS fragments) depends mainly on their CS fragments. Isoselective inhibitors have the same affinity trend toward different enzymes of the same family with a common catalytic mechanism. Thus, very good correlation between experimentally determined and theoretically calculated Ki values was demonstrated. A practical outcome is the application of the described method as a tool for an expert analysis in virtual screening of inhibitor libraries and in the design of new enzyme inhibitors.
authors.affiliation: The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ozeri
authors.forename: Netaly
authors.initials: N
authors.lastname: Khazanov
authors.forename: Nurit
authors.initials: N
authors.lastname: Perlman
authors.forename: Michael
authors.initials: M
authors.lastname: Shokhen
authors.forename: Amnon
authors.initials: A
authors.lastname: Albeck
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors