Open AccessMolecular Modeling Studies on NADP-Dependence of Candida Tropicalis Strain Xylose Reductase
Author(s) -
Jingfang Wang,
DongQing Wei,
Hongli Du,
Yixue Li,
KuoChen Chou
Publication year - 2008
Publication title -
the open bioinformatics journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.259
H-Index - 8
ISSN - 1875-0362
DOI - 10.2174/1875036200802010072
Subject(s) - nad+ kinase , aldose reductase , candida tropicalis , biochemistry , xylose , stereochemistry , aldo keto reductase , aldehyde reductase , cofactor , reductase , chemistry , strain (injury) , saccharomyces cerevisiae , enzyme , biology , yeast , fermentation , anatomy
The Candida tropicalis strain CT1799 xylose reductase (XR) with protein ID ABG49458.1 is a kind ofNADPH-dependent xylose reductase. It could be used to construct recombinant Saccharomyces cerevisiae strain for utilizingxylose and producing alcohol. To investigate the interaction mechanism of XR with NADP and NAD, the 3D (dimensional)structure for XR was developed. With the 3D structure, the molecular docking operations were conducted to findthe most favorable bindings of XR with NADP and NAD. Based on these results, the binding pockets of XR for NADPand NAD have been explicitly defined, respectively. It was observed that Asn278 and Arg282 of XR could form hydrogenbonds with both NADP and NAD that were bonded to the same site of XR with some competitive relationship. However,according to the binding energies and conformational fitting, NADP is a more favorable coenzyme to XR. All these findingsmay explain why XR is NADP-dependent. The findings can be used to guide mutagenesis studies, providing usefulclues to modify the enzyme for improving the utilization of xylose in producing alcohol. In addition, because the humanaldose reductases have the functions to reduce the open chain form of glucose to sorbitol, a process physiologically significantfor diabetic patients at the time that their blood glucose levels are elevated, the information gained through thisstudy may also stimulate the development of new strategies for the therapeutic treatment of diabetes.