In:
ChemBioChem, Wiley, Vol. 5, No. 2 ( 2004-02-06), p. 214-223
Abstract:
Molecular modeling with classical force‐fields has been used to study the reactant complex and the tetrahedral intermediate in lipase‐catalyzed ester hydrolysis in 20 enzyme/substrate combinations. The R and S enantiomers of α‐methyldecanoic acid ester served as substrates for the wild‐type lipase from Pseudomonas aeruginosa and nine selected mutants. After suitable preparation of initial structures from an available wild‐type crystal structure, each system was subjected to 1 ns CHARMM force‐field molecular dynamics simulations. The resulting geometric and energetic changes allow interpretation of some experimentally observed effects of mutations, particularly with regard to the “hot spots” at residues 155 and 162. The replacement S155F enhances S enantiopreference through a steric relay involving Leu162. The double mutation S53P + L162G improves S enantioselectivity by creating a new binding pocket for the S enantiomer with an additional stabilizing hydrogen bond to His83. The simulations provide insight into remote and cooperative effects of mutations.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.200300731
Language:
English
Publisher:
Wiley
Publication Date:
2004
detail.hit.zdb_id:
2020469-3
SSG:
12