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An N⋯H⋯N low-barrier hydrogen bond preorganizes the catalytic site of aspartate aminotransferase to facilitate the second half-reaction

Victoria N. Drago, Steven Dajnowicz, Jerry M. Parks, Matthew P. Blakeley, David A. Keen, Nicolas Coquelle, Kevin L. Weiss, Oksana Gerlits, Andrey Kovalevsky, Timothy C. Mueser

2022Chemical Science20 citationsDOIOpen Access PDF

Abstract

and catalytic Lys258 Nζ amino groups an equally shared deuterium is observed in an apparent low-barrier hydrogen bond (LBHB). Density functional theory calculations were performed to provide further evidence of this LBHB interaction. The structural arrangement and the juxtaposition of PMP and Lys258, facilitated by the LBHB, suggests active site preorganization for the incoming ketoacid substrate that initiates the second half-reaction.

Topics & Concepts

CatalysisChemistryActive siteHydrogen bondPyridoxalPyridoxamineEnzymePyridoxal phosphatePhosphateStereochemistryBiochemistryMoleculeOrganic chemistryCofactorEnzyme Structure and FunctionAmino Acid Enzymes and MetabolismBiochemical and Molecular Research
An N⋯H⋯N low-barrier hydrogen bond preorganizes the catalytic site of aspartate aminotransferase to facilitate the second half-reaction | Litcius