GH47 and Other Glycoside Hydrolases Catalyze Glycosidic Bond Cleavage with the Assistance of Substrate Super-arming at the Transition State.

ABSTRACT: Super-armed glycosyl donors, whose substituents are predominantly held in pseudoaxial positions, exhibit strongly increased reactivity in glycosylation through significant stabilization of oxocarbenium-like transition states. Examination of X-ray crystal structures reveals that the GH47 family of glycoside hydrolases have evolved so as to distort their substrates away from the ground state conformation in such a manner as to present multiple C-O bonds in pseudoaxial positions and so benefit from conformational super-arming of their substrates, thereby enhancing catalysis. Through analysis of literature mutagenic studies, we show that a suitably placed aromatic residue in GHs 6 and 47 sterically enforces super-armed conformations on their substrates. GH families 45, 81, and 134 on the other

SUBMITTER: Quirke JCK 

PROVIDER: S-EPMC8579916 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature