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Structural basis for the β‐lactamase activity of EstU1, a family VIII carboxylesterase
Author(s) -
Cha SunShin,
An Young Jun,
Jeong ChangSook,
Kim MinKyu,
Jeon Jeong Ho,
Lee ChangMuk,
Lee Hyun Sook,
Kang Sung Gyun,
Lee JungHyun
Publication year - 2013
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24334
Subject(s) - carboxylesterase , hydrolysis , peptide bond , amide , chemistry , active site , stereochemistry , substrate (aquarium) , lactam , catalysis , combinatorial chemistry , benzimidazole , antibiotics , enzyme , biochemistry , organic chemistry , biology , ecology
ABSTRACT EstU1 is a unique family VIII carboxylesterase that displays hydrolytic activity toward the amide bond of clinically used β‐lactam antibiotics as well as the ester bond of p ‐nitrophenyl esters. EstU1 assumes a β‐lactamase‐like modular architecture and contains the residues Ser100, Lys103, and Tyr218, which correspond to the three catalytic residues (Ser64, Lys67, and Tyr150, respectively) of class C β‐lactamases. The structure of the EstU1/cephalothin complex demonstrates that the active site of EstU1 is not ideally tailored to perform an efficient deacylation reaction during the hydrolysis of β‐lactam antibiotics. This result explains the weak β‐lactamase activity of EstU1 compared with class C β‐lactamases. Finally, structural and sequential comparison of EstU1 with other family VIII carboxylesterases elucidates an operative molecular strategy used by family VIII carboxylesterases to extend their substrate spectrum. Proteins 2013; 81:2045–2051. © 2013 Wiley Periodicals, Inc.