Adenine binding mode is a key factor in triggering the early release of NADH in coenzyme A-dependent methylmalonate semialdehyde dehydrogenase.

ABSTRACT: Structural dynamics associated with cofactor binding have been shown to play key roles in the catalytic mechanism of hydrolytic NAD(P)-dependent aldehyde dehydrogenases (ALDH). By contrast, no information is available for their CoA-dependent counterparts. We present here the first crystal structure of a CoA-dependent ALDH. The structure of the methylmalonate semialdehyde dehydrogenase (MSDH) from Bacillus subtilis in binary complex with NAD(+) shows that, in contrast to what is observed for hydrolytic ALDHs, the nicotinamide ring is well defined in the electron density due to direct and H(2)O-mediated hydrogen bonds with the carboxamide. The structure also reveals that a conformational isomerization of the NMNH is possible in MSDH, as shown for hydrolytic ALDHs. Finally, the adenine ring i

SUBMITTER: Bchini R 

PROVIDER: S-EPMC3438941 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature