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

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.