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A Molecular Mechanism of Enantiorecognition of Tertiary Alcohols by Carboxylesterases
Author(s) -
Henke Erik,
Bornscheuer Uwe T.,
Schmid Rolf D.,
Pleiss Jürgen
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200200518
Subject(s) - esterase , chemistry , stereochemistry , substrate (aquarium) , bacillus subtilis , hydrolysis , enantiomer , enzyme , alanine , mutant , amino acid , biochemistry , biology , ecology , genetics , bacteria , gene
Carboxylesterases containing the sequence motif GGGX catalyze the hydrolysis of esters of chiral tertiary alcohols, albeit with only low to moderate enantioselectivity, for three model substrates (linalyl acetate, methyl‐1‐pentin‐1‐yl acetate, 2phenyl‐3‐butin‐2‐yl acetate). In order to understand the molecular mechanism of enantiorecognition and to improve enantioselectivity for this interesting substrate class, the interaction of both enantiomers with the substrate binding sites of acetylcholinesterases and p ‐nitrobenzyl esterase from Bacillus subtilis was modeled and correlated to experimental enantioselectivity. For all substrate–enzyme pairs, enantiopreference and ranking by enantioselectivity could be predicted by the model. In p ‐nitrobenzyl esterase, one of the key residues in determining enantioselectivity was G105: exchange of this amino acid for an alanine residue led to a sixfold increase of enantioselectivity ( E =19) towards 2phenyl‐3‐butin‐2‐yl acetate. However, the effect of this mutation is specific: the same mutant had the opposite enantiopreference towards the substrate linalyl acetate. Thus, depending on the substrate structure, the same mutant has either increased enantioselectivity or opposite enantiopreference compared to the wild‐type enzyme.

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