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Differences in nucleotide specificity and catalytic mechanism betweenVibrio harveyialdehyde dehydrogenase and other members of the aldehyde dehydrogenase superfamily

Chemico-Biological Interactions
Publication Date
DOI: 10.1016/s0009-2797(00)00219-2
  • V. Harveyi Aldh
  • General Base
  • Nadp+Specificity


Abstract The fatty aldehyde dehydrogenase (Vh-ALDH) isolated from the luminescent bacterium, Vibrio harveyi, differs from other aldehyde dehydrogenases in its high affinity for NADP +. The binding of NADP + appears to arise from the interaction of the 2′-phosphate of the adenosine moiety of NADP + with a threonine (T175) in the nucleotide recognition site just after the β B strand as well as with an arginine (R210) that pi stacks over the adenosine moiety. The active site of Vh-ALDH contains the usual suspects of a cysteine (C289), two glutamates (E253 and E377) and an asparagine (N147) involved in the aldehyde dehydrogenase mechanism. However, Vh-ALDH has one polar residue in the active site that distinguishes it from other ALDHs; a histidine (H450) is in close contact with the cysteine nucleophile. As a glutamate has been implicated in promoting the nucleophilicity of the active site cysteine residue in ALDHs, the close contact of a histidine with the cysteine nucleophile in Vh-ALDH raises the possibility of alternate routes to increase the reactivity of the cysteine nucleophile. The effects of mutation of these residues on the different functions catalyzed by Vh-ALDH including acylation, (thio)esterase, reductase and dehydrogenase activities should help define the specific roles of the residues in the active site of ALDHs.

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