Decreased Transition-State Analogue Affinity in Isotopically Heavy MTAN with Increased Catalysis.

ABSTRACT: 5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase from Helicobacter pylori (HpMTAN) demonstrated faster chemistry when expressed as an isotopically heavy protein, with ²H, ¹³C, and ¹⁵N replacing the bulk of normal isotopes. The inverse heavy enzyme isotope effect has been attributed to improved enzyme-reactant interactions causing more frequent transition-state formation ( Proc. Natl. Acad. Sci. U.S.A. 2021, 118, e2109118118). Transition-state analogues stabilize the transient dynamic geometry of the transition state and inform on transition-state dynamics. Here, a slow-onset, tight-binding transition-state analogue of HpMTAN is characterized with heavy and light enzymes. Dissociation constants for the initial enc

SUBMITTER: Brown M 

PROVIDER: S-EPMC10636763 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature