期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 505, 期 1, 页码 33-41出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2010.10.010
关键词
FEP; BIE; QM/MM; Isoforms; LDH
资金
- Ministry of Science and Higher Education, Poland [NN204/1579/33]
We present QM/MM calculations that show differences in geometries of active sites of M-4 and H-4 isoforms of human LDH ligated with oxamate, pyruvate or L-lactate. As the consequence of these differences, binding isotope effects of the methyl hydrogen atoms of pyruvate and L-lactate may be used to experimentally distinguish these isoforms. Based on the FEP calculations we argue that L-lactate is a better candidate for the experimental studies. Our calculations of energies of interactions of ligands with the active site residues provide explanation for the observed experimentally sensitivity to inhibition of the M-4 isoenzyme isoform and pinpoint the differences to interactions of the ligand with the histidine residue. We conclude that pyruvate interacts much stronger in the active site of H-4 than M-4 isoform and that the latter interactions are weaker than with water molecules in the aqueous solution. (C) 2010 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据