Coordination Chemistry Controls Coenzyme B12 Synthesis by Human Adenosine Triphosphate:Cob(I)alamin Adenosyltransferase.
Inorg Chem
; 62(32): 12630-12633, 2023 Aug 14.
Article
en En
| MEDLINE
| ID: mdl-37526260
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 mV more positive than for the five-coordinate (5-c) water-liganded species. The redox potential of MMAB-bound cob(II)alamin is within the range of adrenodoxin, which we demonstrate functions as an electron donor. We also show that stabilization of 5-c cob(II)alamin by a subset of MMAB patient variants compromises the reduction by adrenodoxin, explaining the underlying pathogenic mechanism.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenosina Trifosfato
/
Adrenodoxina
Límite:
Humans
Idioma:
En
Revista:
Inorg Chem
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos