RESEARCH ARTICLE


Molecular Modeling Studies on NADP-Dependence of Candida Tropicalis Strain Xylose Reductase



Jing-Fang Wang2, Dong-Qing Wei*, 1, 4, Hong-Li Du3, Yi-Xue, Li1, 2, Kuo-Chen Chou1, 4
1 College of life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China
2 Bioinformatics Center, Key Lab of System Biology, Shanghai Institutes for Biological Sciences, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3 School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510640, China
4 Gordon Life Science Institute, San Diego, California, USA


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Creative Commons License
© 2008 Wang et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the College of life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China; E-mail: dqwei@sjtu.edu.cn Gordon Life Science Institute, San Diego, California, USA; E-mail: lifescience@san.rr.com


Abstract

The Candida tropicalis strain CT1799 xylose reductase (XR) with protein ID ABG49458.1 is a kind of NADPH-dependent xylose reductase. It could be used to construct recombinant Saccharomyces cerevisiae strain for utilizing xylose 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 find the most favorable bindings of XR with NADP and NAD. Based on these results, the binding pockets of XR for NADP and NAD have been explicitly defined, respectively. It was observed that Asn278 and Arg282 of XR could form hydrogen bonds 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 findings may explain why XR is NADP-dependent. The findings can be used to guide mutagenesis studies, providing useful clues to modify the enzyme for improving the utilization of xylose in producing alcohol. In addition, because the human aldose reductases have the functions to reduce the open chain form of glucose to sorbitol, a process physiologically significant for diabetic patients at the time that their blood glucose levels are elevated, the information gained through this study may also stimulate the development of new strategies for the therapeutic treatment of diabetes.

Keywords: New strategy of diabetes therapy, Alcohol-producing, Xylose reductase, Assimilation, Binding pocket, Hydrogen bonds.