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Stereoselectivity and Expanded Substrate Scope of an Engineered PLP‐Dependent Aldolase
Author(s) -
Seebeck Florian P.,
Guainazzi Angelo,
Amoreira Celine,
Baldridge Kim K.,
Hilvert Donald
Publication year - 2006
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200602529
Subject(s) - aldolase a , active site , chemistry , docking (animal) , stereoselectivity , stereochemistry , pyridoxal phosphate , enzyme , substrate specificity , pyridoxal , substrate (aquarium) , combinatorial chemistry , directed evolution , biochemistry , catalysis , mutant , biology , cofactor , ecology , medicine , nursing , gene
Optimizing the active site : A pyridoxal 5′‐phosphate(PLP)‐dependent alanine racemase was converted into a retro‐aldolase by a single active‐site mutation. This new catalyst reacts efficiently with quaternary β‐hydroxy α‐amino acids, a class of molecules that natural aldolases have not been evolved to handle. Computational docking experiments suggest a novel mechanism for this process and rationalize the stereochemical preferences of the enzyme.