RT Journal Article
SR Electronic
T1 Cofactor selectivity in methylmalonyl-CoA mutase, a model cobamide-dependent enzyme
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 637140
DO 10.1101/637140
A1 Olga M. Sokolovskaya
A1 Kenny C. Mok
A1 Jong Duk Park
A1 Jennifer L. A. Tran
A1 Kathryn A. Quanstrom
A1 Michiko E. Taga
YR 2019
UL http://biorxiv.org/content/early/2019/05/21/637140.abstract
AB Cobamides, a uniquely diverse family of enzyme cofactors related to vitamin B12, are produced exclusively by bacteria and archaea but used in all domains of life. While it is widely accepted that cobamide-dependent organisms require specific cobamides for their metabolism, the biochemical mechanisms that make cobamides functionally distinct are largely unknown. Here, we examine the effects of cobamide structural variation on a model cobamide-dependent enzyme, methylmalonyl-CoA mutase (MCM). The in vitro binding affinity of MCM for cobamides can be dramatically influenced by small changes in the structure of the lower ligand of the cobamide, and binding selectivity differs between bacterial orthologs of MCM. In contrast, variations in the lower ligand have minor effects on MCM catalysis. Bacterial growth assays demonstrate that cobamide requirements of MCM in vitro largely correlate with in vivo cobamide dependence. This result underscores the importance of enzyme selectivity in the cobamide-dependent physiology of bacteria.