1a80
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NATIVE 2,5-DIKETO-D-GLUCONIC ACID REDUCTASE A FROM CORYNBACTERIUM SP. COMPLEXED WITH NADPH
OverviewOverview
The three-dimensional structure of Corynebacterium 2, 5-diketo-D-gluconic, acid reductase A (2,5-DKGR A; EC 1.1.1.-), in complex with cofactor NADPH, has been solved by using x-ray crystallographic data to 2.1-A resolution., This enzyme catalyzes stereospecific reduction of 2,5-diketo-D-gluconate, (2,5-DKG) to 2-keto-L-gulonate. Thus the three-dimensional structure has, now been solved for a prokaryotic example of the aldo-keto reductase, superfamily. The details of the binding of the NADPH cofactor help to, explain why 2,5-DKGR exhibits lower binding affinity for cofactor than the, related human aldose reductase does. Furthermore, changes in the local, loop structure near the cofactor suggest that 2,5-DKGR will not exhibit, the biphasic cofactor binding characteristics observed in aldose, reductase. Although the crystal structure does not include substrate, the, two ordered water molecules present within the substrate-binding pocket, are postulated to provide positional landmarks for the substrate 5-keto, and 4-hydroxyl groups. The structural basis for several previously, described active-site mutants of 2,5-DKGR A is also proposed. Recent, research efforts have described a novel approach to the synthesis of, L-ascorbate (vitamin C) by using a genetically engineered microorganism, that is capable of synthesizing 2,5-DKG from glucose and subsequently is, transformed with the gene for 2,5-DKGR. These modifications create a, microorganism capable of direct production of 2-keto-L-gulonate from, D-glucose, and the gulonate can subsequently be converted into vitamin C., In economic terms, vitamin C is the single most important specialty, chemical manufactured in the world. Understanding the structural, determinants of specificity, catalysis, and stability for 2,5-DKGR A is of, substantial commercial interest.
About this StructureAbout this Structure
1A80 is a Single protein structure of sequence from Corynebacterium sp. with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of 2,5-diketo-D-gluconic acid reductase A complexed with NADPH at 2.1-A resolution., Khurana S, Powers DB, Anderson S, Blaber M, Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6768-73. PMID:9618487
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