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Yamamoto, K and Wilson, DK (2013) Identification, characterization, and crystal structure of an aldo-keto reductase (AKR2E4) from the silkworm Bombyx mori. Arch. Biochem. Biophys. 538:156-63


A 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 1.3Å resolution to elucidate substrate binding and catalysis. The enzyme is a 33-kDa monomer and reduces dicarbonyl compounds such as isatin and 17α-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 (β/α)8-barrel, and residues involved in catalysis are conserved.


PubMed Online version:10.1016/j.abb.2013.08.018


Alcohol Oxidoreductases/chemistry; Alcohol Oxidoreductases/metabolism; Amino Acid Sequence; Animals; Bombyx/chemistry; Bombyx/enzymology; Bombyx/metabolism; Catalytic Domain; Crystallography, X-Ray; Ecdysone/analogs & derivatives; Ecdysone/metabolism; Hemolymph/enzymology; Models, Molecular; Molecular Sequence Data; NAD/metabolism; NADP/metabolism; Oxidation-Reduction; Protein Conformation; Sequence Alignment; Substrate Specificity



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0004033: aldo-keto reductase (NADP) activity




Figure 2 shows sequence and structural homology to other defined aldo-keto reductases, notably human aldo-keto reductase AKR1C2.

CACAO 9976

See also


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