Crystallographic evidence for active-site dynamics in the hydrolytic aldehyde dehydrogenases. Implications for the deacylation step of the catalyzed reaction
Por:
Munoz-Clares, RA, Gonzalez-Segura, L, Diaz-Sanchez, AG
Publicada:
30 may 2011
Categoría:
Toxicology
Resumen:
The overall chemical mechanism of the reaction catalyzed by the hydrolytic aldehyde dehydrogenases (ALDHs) involves three main steps: (1) nucleophilic attack of the thiol group of the catalytic cysteine on the carbonyl carbon of the aldehyde substrate; (2) hydride transfer from the tetrahedral thiohemiacetal intermediate to the pyridine ring of NAD(P)(+); and (3) hydrolysis of the resulting thioester intermediate (deacylation). Crystal structures of different ALDHs from several organisms-determined in the absence and presence of bound NAD(P)(+), NAD(P)H, aldehydes, or acid products-showed specific details at the atomic level about the catalytic residues involved in each of the catalytic steps. These structures also showed the conformational flexibility of the nicotinamide half of the cofactor, and of the catalytic cysteinyl and glutamyl residues, the latter being the general base that activates the hydrolytic water molecule in the deacylation step. The architecture of the ALDH active s
Filiaciones:
Munoz-Clares, RA:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Bioquim, Mexico City 04510, DF, Mexico
Gonzalez-Segura, L:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Bioquim, Mexico City 04510, DF, Mexico
Diaz-Sanchez, AG:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Bioquim, Mexico City 04510, DF, Mexico
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