The crystal structure of rat liver AKR7A1: a dimeric member of the Aldo-Keto reductase superfamily

E. Kozma, E. Brown, E. Ellis, A. Lapthorn

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)16285-16293
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
Publication statusPublished - 2002

Keywords

  • biological chemistry
  • rat liver
  • cofactor binding

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