5ucd
Benzaldehyde Dehydrogenase, a Class 3 Aldehyde Dehydrogenase, with bound NADP+ and Benzoate Adduct
Structural highlights
FunctionMDLD_PSEPU NAD or NADP-dependent benzaldehyde dehydrogenase that catalyzes the conversion of benzaldehyde into benzoate in the (R)-mandelate degradation pathway.[1] Publication Abstract from PubMedBenzaldehyde dehydrogenase from Pseudomonas putida (PpBADH) belongs to the Class 3 aldehyde dehydrogenase (ALDH) family. The Class 3 ALDHs are unusual in that they are generally dimeric (rather than tetrameric), relatively non-specific and utilize both NAD+ and NADP+. To date, X-ray structures of three Class 3 ALDHs have been determined, of which only two have cofactor bound, both in the NAD+ form. Here we report the crystal structure of PpBADH in complex with NADP+ and a thioacyl intermediate adduct. The overall architecture of PpBADH resembles that of most other members of the ALDH superfamily, and the cofactor binding residues are well conserved. Conversely, the pattern of cofactor binding for the rat Class 3 ALDH differs from that of PpBADH and other ALDHs. This has been interpreted in terms of a different mechanism for the rat enzyme. Comparison with the PpBADH structure, as well as multiple sequence alignments, suggest that one of two conserved glutamates, at positions 215 (209 in rat) and 337 (333 in rat), would act as the general base necessary to hydrolyze the thioacyl intermediate. While the latter is the general base in the rat Class 3 ALDH, site-specific mutagenesis indicates that Glu215 is the likely candidate for PpBADH, a result more typical of the Class 1 and 2 ALDH families. Finally, this study shows that hydride transfer is not rate limiting, lending further credence to the suggestion that PpBADH is more similar to the Class 1 and 2 ALDHs than it is to other Class 3 ALDHs. Structure and mechanism of benzaldehyde dehydrogenase from Pseudomonas putida ATCC 12633, a member of the Class 3 aldehyde dehydrogenase superfamily.,Zahniser MP, Prasad S, Kneen MM, Kreinbring CA, Petsko GA, Ringe D, McLeish MJ Protein Eng Des Sel. 2017 Mar 9:1-8. doi: 10.1093/protein/gzx015. PMID:28338942[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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