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Structural basis for the β-lactamase activity of EstU1, a family VIII carboxylesterase

Authors :
Chang-Sook Jeong
Jung-Hyun Lee
Chang-Muk Lee
Young Jun An
Hyun Sook Lee
Min-Kyu Kim
Jeong Ho Jeon
Sung Gyun Kang
Sun-Shin Cha
Source :
Proteins: Structure, Function, and Bioinformatics. 81:2045-2051
Publication Year :
2013
Publisher :
Wiley, 2013.

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.

Details

ISSN :
08873585
Volume :
81
Database :
OpenAIRE
Journal :
Proteins: Structure, Function, and Bioinformatics
Accession number :
edsair.doi...........5d49a1366fcd5398381424561a916f2c
Full Text :
https://doi.org/10.1002/prot.24334