Molecular modeling of substrate binding in wild‐type and mutant Corynebacteria 2,5‐diketo‐D‐gluconate reductases

@article{Khurana2000MolecularMO,
  title={Molecular modeling of substrate binding in wild‐type and mutant Corynebacteria 2,5‐diketo‐D‐gluconate reductases},
  author={Sumit Khurana and Gulsah Sanli and David B. Powers and Susan Anderson and Michael Blaber},
  journal={Proteins: Structure},
  year={2000},
  volume={39}
}
2,5‐Diketo‐D‐gluconic acid reductase (2,5‐DKGR; E.C. 1.1.1.‐) catalyzes the Nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent stereo‐specific reduction of 2,5‐diketo‐D‐gluconate (2,5‐DKG) to 2‐keto‐L‐gulonate (2‐KLG), a precursor in the industrial production of vitamin C (L‐ascorbate). Microorganisms that naturally ferment D‐glucose to 2,5‐DKG can be genetically modified to express the gene for 2,5‐DKGR, and thus directly produce vitamin C from D‐glucose. Two naturally occurring… 
Structural alteration of cofactor specificity in Corynebacterium 2,5‐diketo‐D‐gluconic acid reductase
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The structural basis of the differential NAD(P)H selectivity of wild‐type and mutant 2,5‐DKGR enzymes has been identified and an X‐ray crystal structure of the holo form of this mutant in complex with NADH cofactor is reported, as well as thermodynamic stability data.
Alteration of the specificity of the cofactor-binding pocket of Corynebacterium 2,5-diketo-D-gluconic acid reductase A.
TLDR
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Details of the structural biology and molecular dynamics associated with catalysis, cofactor, and substrate binding as elucidated for those AKRs for which apo- and holo-structures are available are focused on.
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The three-dimensional structure of Corynebacterium 2, 5-diketo-D-gluconic acid reductase A, in complex with cofactor NADPH, has been solved by using x-ray crystallographic data to 2.1-A resolution and 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 reduct enzyme.
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