Premium
Computer modeling of substrate binding to lipases from Rhizomucor miehei, Humicola lanuginosa , and Candida rugosa
Author(s) -
Norin Martin,
Haeffner Fredrik,
Achour Adnane,
Norin Torbjörn,
Hult Karl
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560030915
Subject(s) - candida rugosa , rhizomucor miehei , substrate (aquarium) , lipase , chemistry , microbiology and biotechnology , enzyme , biology , biochemistry , triacylglycerol lipase , ecology
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.