The structure of the rat liver aflatoxin dialdehyde reductase (AKR7A1) has been solved to 1.38î.. resolution. Although it shares a similar a/b barrel structure with other members of the aldo-keto reductase superfamily, AKR7A1 is the first dimeric member to be crystallised. The crystal structure also reveals details of the ternary complex as one subunit of the dimer contains NADP+ and the inhibitor citrate. Although the underlying catalytic mechanism appears similar to other aldo-keto reductases, the substrate-binding pocket contains several charged amino acids (Arg-231 and Arg-327) that distinguish it from previously characterised aldo-keto reductases with respect to size and charge. These differences account for the substrate specificity for 4-carbon acid-aldehydes such as succinic semialdehyde and 2-carboxybenzaldehyde, as well as for the idiosyncratic substrate aflatoxin B1 dialdehyde of this subfamily of enzymes. Structural differences between the AKR7A1 ternary complex and apo-enzyme reveal a significant hinged movement of the enzyme involving not only the loops of the structure, but also parts of the a/b barrel most intimately involved in cofactor binding.
- biological chemistry
- rat liver
- cofactor binding
Kozma, E., Brown, E., Ellis, E., & Lapthorn, A. (2002). The crystal structure of rat liver AKR7A1: a dimeric member of the Aldo-Keto reductase superfamily. Journal of Biological Chemistry, 277(18), 16285-16293. https://doi.org/10.1074/jbc.M110808200