Structure of monkey dimeric dihydrodiol dehydrogenase in complex with isoascorbic acid

Vincenzo Carbone, Rie Sumii, Shuhei Ishikura, Yukuhiko Asada, Akira Hara, Ossama El-Kabbani

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6 Citations (Scopus)

Abstract

Mammalian dimeric dihydrodiol dehydrogenase (DD) is identical to NADP(+)-dependent D-xylose dehydrogenase. A recent investigation showed that the three-dimensional structure of monkey DD is similar to those of prokaryotic NADP(H)-dependent glucose-fructose oxidoreductase (GFO) and 1,5-anhydro-d-fructose reductase (AFR); however, it differs in coenzyme-binding and catalytic residues. Dimeric DD has a high affinity for NADP(H) when compared with AFR and differs from both GFO and AFR in its specificity for sugars and hydrophobic xenobiotic compounds as substrates. The crystal structure of monkey dimeric DD complexed with the inhibitor isoascorbic acid has been determined at 2.59 angstrom resolution. Molecular modelling of coenzyme binding complemented with site-directed mutagenesis has been utilized to propose a binding mode for the coenzyme molecule and to gain insights into the roles of the residues comprising the active site and coenzyme-binding domain of DD. Several key residues have been identified within the coenzyme-binding domain, including Arg37, Arg41, His76 and His79, that contribute to the high affinity for coenzyme.
Original languageEnglish
Pages (from-to)532 - 542
Number of pages11
JournalActa Crystallographica Section D: Biological Crystallography
Volume64
Issue numberPart 5
Publication statusPublished - 2008

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