3wcz
Crystal structure of Bombyx mori aldo-keto reductase (AKR2E4) in complex with NADP
Structural highlights
FunctionAK2E4_BOMMO NADP-dependent oxidoreductase with high 3-dehydroecdysone reductase activity. May play a role in the regulation of molting. Has lower activity with phenylglyoxal and isatin (in vitro). Has no activity with NADH as cosubstrate. Has no activity with nitrobenzaldehyde and 3-hydroxybenzaldehyde.[1] Publication Abstract from PubMedA new member of the aldo-keto reductase (AKR) superfamily with 3-dehydroecdysone reductase activity was found in the silkworm Bombyx mori upon induction by the insecticide diazinon. The amino acid sequence showed that this enzyme belongs to the AKR2 family, and the protein was assigned the systematic name AKR2E4. In this study, recombinant AKR2E4 was expressed, purified to near homogeneity, and kinetically characterized. Additionally, its ternary structure in complex with NADP(+) and citrate was refined at 1.3A resolution to elucidate substrate binding and catalysis. The enzyme is a 33-kDa monomer and reduces dicarbonyl compounds such as isatin and 17alpha-hydroxy progesterone using NADPH as a cosubstrate. No NADH-dependent activity was detected. Robust activity toward the substrate inhibitor 3-dehydroecdysone was observed, which suggests that this enzyme plays a role in regulation of the important molting hormone ecdysone. This structure constitutes the first insect AKR structure determined. Bound NADPH is located at the center of the TIM- or (beta/alpha)8-barrel, and residues involved in catalysis are conserved. Identification, characterization, and crystal structure of an aldo-keto reductase (AKR2E4) from the silkworm Bombyx mori.,Yamamoto K, Wilson DK Arch Biochem Biophys. 2013 Oct 15;538(2):156-63. doi: 10.1016/j.abb.2013.08.018. , Epub 2013 Sep 6. PMID:24012638[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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