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

ABSTRACT: Pyridoxal 5'-phosphate (PLP)-dependent enzymes have been extensively studied for their ability to fine-tune PLP cofactor electronics to promote a wide array of chemistries. Neutron crystallography offers a straightforward approach to studying the electronic states of PLP and the electrostatics of enzyme active sites, responsible for the reaction specificities, by enabling direct visualization of hydrogen atom positions. Here we report a room-temperature joint X-ray/neutron structure of aspartate aminotransferase (AAT) with pyridoxamine 5'-phosphate (PMP), the cofactor product of the first half reaction catalyzed by the enzyme. Between PMP N_SB and catalytic Lys258 Nζ amino groups an equally shared deuterium is observed in an apparent low-barrier hydrogen bond (LBHB). Density func

SUBMITTER: Drago VN 

PROVIDER: S-EPMC9430417 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature