Comparative analysis of binding affinities between styrene and mammalian CYP2E1 by bioinformatics approaches

TY - JOUR

T1 - Comparative analysis of binding affinities between styrene and mammalian CYP2E1 by bioinformatics approaches

AU - Wu, Bing

AU - Sun, Jie

AU - Cheng, Shu Pei

AU - Gu, Ji Dong

AU - Li, Ai Min

AU - Zhang, Xu Xiang

N1 - Funding Information: Acknowledgments This research work was financially supported by National Natural Science Foundation of China (No. 50938004), Social Development Foundation of Jiangsu Province (No. BE2009668) and State Water Pollution Control and Treatment Technique Program (No. 2008ZX07528-005).

PY - 2011/7

Y1 - 2011/7

N2 - Abstract:: Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme involved in styrene metabolism. This study compared the binding affinities between styrene and 11 mammalian CYP2E1 systems using bioinformatics methods. Firstly, amino acid sequences of CYP2E1s were obtained from the Swiss-Prot database. Then, taking the crystal structure of human CYP2E1 as a template, 3D models of the CYP2E1s of other mammals were constructed using the SWISS-MODEL program. Finally, the generated homology models were applied to calculate their docking capacities against styrene and polystyrene using the Surflex-Dock program, which could automatically dock ligands into a receptor's ligand binding site using a protomol based approach and assess the affinity by an empirically derived scoring function. Docking experiments showed that the studied mammalian CYP2E1s had high binding affinities with styrene. For polystyrene, the dimmer of styrene has high binding affinities with CYP2E1s, however, trimer and other high polymers were found hard to be docked into the CYP2E1s. The results of this study indicated that bioinformatics approaches might be useful tools to predict styrene and polystyrene affinities with mammalian CYP2E1s.

AB - Abstract:: Cytochrome P450 2E1 (CYP2E1) is a cytochrome P450 enzyme involved in styrene metabolism. This study compared the binding affinities between styrene and 11 mammalian CYP2E1 systems using bioinformatics methods. Firstly, amino acid sequences of CYP2E1s were obtained from the Swiss-Prot database. Then, taking the crystal structure of human CYP2E1 as a template, 3D models of the CYP2E1s of other mammals were constructed using the SWISS-MODEL program. Finally, the generated homology models were applied to calculate their docking capacities against styrene and polystyrene using the Surflex-Dock program, which could automatically dock ligands into a receptor's ligand binding site using a protomol based approach and assess the affinity by an empirically derived scoring function. Docking experiments showed that the studied mammalian CYP2E1s had high binding affinities with styrene. For polystyrene, the dimmer of styrene has high binding affinities with CYP2E1s, however, trimer and other high polymers were found hard to be docked into the CYP2E1s. The results of this study indicated that bioinformatics approaches might be useful tools to predict styrene and polystyrene affinities with mammalian CYP2E1s.

KW - Cytochrome P450 2E1

KW - Homology modeling

KW - Mammal

KW - Molecular docking

KW - Styrene

UR - http://www.scopus.com/inward/record.url?scp=79960333804&partnerID=8YFLogxK

U2 - 10.1007/s10646-011-0643-z

DO - 10.1007/s10646-011-0643-z

M3 - 文章

C2 - 21424721

AN - SCOPUS:79960333804

SN - 0963-9292

VL - 20

SP - 1041

EP - 1046

JO - Ecotoxicology

JF - Ecotoxicology

IS - 5

ER -