title: Stereoelectronic requirements for optimal hydrogen-bond-catalyzed enolization.
abstract: Protein crystallographic analysis of the active sites of enolizing enzymes and structural analysis of hydrogen-bonded carbonyl compounds in small molecule crystal structures, complemented by quantum chemical calculations on related model enolization reactions, suggest a new stereoelectronic model that accounts for the observed out-of-plane orientation of hydrogen-bond donors (HBDs) in the oxyanion holes of enolizing enzymes. The computational results reveal that the lone-pair directionality of HBDs characteristic for hydrogen-bonded carbonyls is reduced upon enolization, and the enolate displays almost no directional preference for hydrogen bonding. Positioning the HBDs perpendicular to the carbonyl plane induces strain in the catalyst-substrate complex, which is released upon enolization, resulting in more favorable kinetics and thermodynamics than the in-plane arrangement of HBDs.
authors.affiliation: Department of Theoretical Chemistry, Chemical Research Center of the Hungarian Academy of Sciences, Pusztaszeri ut 59-67, H-1025 Budapest, Hungary. papai@chemres.hu
authors.forename: Imre
authors.initials: I
authors.lastname: Pápai
authors.forename: Andrea
authors.initials: A
authors.lastname: Hamza
authors.forename: Petri M
authors.initials: PM
authors.lastname: Pihko
authors.forename: Rik K
authors.initials: RK
authors.lastname: Wierenga
mesh_terms: D000465:Algorithms; D019748:Carbon-Carbon Double Bond Isomerases / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D006860:Hydrogen Bonding; D007659:Ketones / Q000737:chemistry*; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D007659:Ketones; D019748:Carbon-Carbon Double Bond Isomerases