Coordination Chemistry Controls Coenzyme B₁₂ Synthesis by Human Adenosine Triphosphate:Cob(I)alamin Adenosyltransferase.

ABSTRACT: Cobalamin (or vitamin B₁₂)-dependent enzymes and trafficking chaperones exploit redox-linked coordination chemistry to control the cofactor reactivity during catalysis and translocation. As the cobalt oxidation state decreases from 3+ to 1+, the preferred cobalamin geometry changes from six- to four-coordinate (4-c). In this study, we reveal the sizable thermodynamic gain that accrues for human adenosine triphosphate (ATP):cob(I)alamin adenosyltransferase (or MMAB) by enforcing an unfavorable 4-c cob(II)alamin geometry. MMAB-bound cob(II)alamin is reduced to the supernucleophilic cob(I)alamin intermediate during the synthesis of 5'-deoxyadenosylcobalamin. Herein, we report the first experimentally determined reduction potential for 4-c cob(II)alamin (-325 ± 9 mV), which is 180 m

SUBMITTER: Gouda H 

PROVIDER: S-EPMC10507449 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature