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Molecular Modeling of Substrate Binding in Wild-type and Mutant Corynebacteria 2,5-diketo-D-gluconate Reductases

Title: Molecular Modeling of Substrate Binding in Wild-type and Mutant Corynebacteria 2,5-diketo-D-gluconate Reductases.
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Name(s): Khurana, Sumit, author
Sanli, Gulsah, author
Powers, David, author
Anderson, Stephen, author
Blaber, Michael, author
Type of Resource: text
Genre: Text
Date Issued: 1999-11-02
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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 variants of DKGR (DKGR A and DKGR B) have been reported. DKGR B exhibits higher specific activity toward 2,5-DKG than DKGR A; however, DKGR A exhibits a greater selectivity for this substrate and significantly higher thermal stability. Thus, a modified form of DKGR, combining desirable properties from both enzymes, would be of substantial commercial interest. In the present study we use a molecular dynamics-based approach to understand the conformational changes in DKGR A as the active site is mutated to include two active site residue changes that occur in the B form. The results indicate that the enhanced kinetic properties of the B form are due, in part, to residue substitutions in the binding pocket. These substitutions augment interactions with the substrate or alter the alignment with respect to the putative proton donor group.
Identifier: FSU_libsubv1_scholarship_submission_1464374853 (IID), 10.1002/(SICI)1097-0134(20000401)39:1<68::AID-PROT7>3.0.CO;2-Y (DOI)
Keywords: molecular dynamics, molecular modeling, aldo-keto reductase, vitamin C, substrate recognition, 2,5-diketo-D-gluconate, L-ascorbate
Publication Note: Publisher's Version also available at http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0134%2820000401%2939:1%3C68::AID-PROT7%3E3.0.CO;2-Y/full
Preferred Citation: Khurana, S. Sanli, G. Powers, D. Anderson, S. & Blaber, M. (2000) Molecular modeling of substrate binding in wild-type and mutant Corynebacteria 2,5-diketo-D-gluconate reductases. PROTEINS: Structure, Function, and Genetics 39:68 –75
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1464374853
Owner Institution: FSU
Is Part Of: Proteins: Structure, Function and Genetics.
Issue: vol. 39

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Khurana, S., Sanli, G., Powers, D., Anderson, S., & Blaber, M. (1999). Molecular Modeling of Substrate Binding in Wild-type and Mutant Corynebacteria 2,5-diketo-D-gluconate Reductases. Proteins: Structure, Function And Genetics. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1464374853