Protein/Solvent Medium Effects on Mg2+-Carboxylate Interactions in Metalloenzymes

被引:10
作者
Babu, C. Satheesan [1 ]
Lim, Carmay [1 ,2 ]
机构
[1] Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan
[2] Natl Tsing Hua Univ, Dept Chem, Hsinchu 300, Taiwan
关键词
RNASE-H DOMAIN; RIBONUCLEASE-H; CRYSTAL-STRUCTURE; ACTIVE-SITE; METAL-ION; MAGNESIUM; DYNAMICS; MG2+;
D O I
10.1021/ja101494m
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We employed umbrella sampling molecular dynamics simulations in explicit water to study the binding of the Mg2+ cofactor to ribonuclease H (RNase H) from three different organisms. We show that the enzyme can differentiate between different Me-binding modes that are nearly equally stable by creating a free-energy barrier between a water-rich mode and a water-depleted mode. Through a comparison with the corresponding free-energy barrier in water, this effect is shown to emanate from the enzymes's three-dimensional architecture and its associated environment. Implications of these protein medium effects in RNase H function and in structure-based drug/molecular design are discussed.
引用
收藏
页码:6290 / +
页数:3
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