The effect of metal ions on the binding of ethanol to human alcohol dehydrogenase beta2beta2.
Molecular docking simulations were performed in this study to investigate the importance of both structural and catalytic zinc ions in the human alcohol dehydrogenase beta(2)beta(2) on substrate binding. The structural zinc ion is not only important in maintaining the structural integrity of the enzyme, but also plays an important role in determining substrate binding. The replacement of the catalytic zinc ion or both catalytic and structural zinc ions with Cu(2+) results in better substrate binding affinity than with the wild-type enzyme. The width of the bottleneck formed by L116 and V294 in the substrate binding pocket plays an important role for substrate entrance. In addition, unfavorable contacts between the substrate and T48 and F93 prevent the substrate from moving too close to the metal ion. The optimal binding position occurs between 1.9 and 2.4 A from the catalytic metal ion.
Liu
Hsuan-Liang
HL
Department of Chemical Engineering, National Taipei University of Technology, No. 12 Sec. 3 Chung-Hsiao E. Road, Taipei, Taiwan 106, ROC. f10894@ntut.edu.tw
Ho
Yih
Y
Hsu
Chia-Ming
CM
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D011720:Pyrazoles / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D002413:Cations, Divalent; D011720:Pyrazoles; C010201:4-iodopyrazole; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D015032:Zinc