COMPUTER MODELING OF SUBSTRATE-BINDING TO LIPASES FROM RHIZOMUCOR-MIEHEI, HUMICOLA-LANUGINOSA, AND CANDIDA-RUGOSA

被引:60
作者
NORIN, M
HAEFFNER, F
ACHOUR, A
NORIN, T
HULT, K
机构
[1] ROYAL INST TECHNOL,DEPT BIOCHEM & BIOTECHNOL,S-10044 STOCKHOLM,SWEDEN
[2] ROYAL INST TECHNOL,DEPT CHEM,S-10044 STOCKHOLM,SWEDEN
关键词
CALCULATION; ENANTIOSELECTIVITY; FREE ENERGY; WATER;
D O I
10.1002/pro.5560030915
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The substrate-binding sites of the triacyl glyceride lipases from Rhizomucor miehei, Humicola lanuginosa, and Candida rugosa were studied by means of computer modeling methods. The space around the active site was mapped by different probes. These calculations suggested 2 separate regions within the binding site. One region showed high affinity for aliphatic groups, whereas the other region was hydrophilic. The aliphatic site should be a binding cavity for fatty acid chains. Water molecules are required for the hydrolysis of the acyl enzyme, but are probably not readily accessible in the hydrophobic interface, in which lipases are acting. Therefore, the hydrophilic site should be important for the hydrolytic activity of the enzyme. Lipases from R. miehei and H. lanuginosa are excellent catalysts for enantioselective resolutions of many secondary alcohols. We used molecular mechanics and dynamics calculations of enzyme-substrate transition-state complexes, which provided information about molecular interactions important for the enantioselectivities of these reactions.
引用
收藏
页码:1493 / 1503
页数:11
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