Structural basis for the ß-lactamase activity of EstU1, a family VIII carboxylesterase.
Proteins
; 81(11): 2045-51, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-23737193
ABSTRACT
EstU1 is a unique family VIII carboxylesterase that displays hydrolytic activity toward the amide bond of clinically used ß-lactam antibiotics as well as the ester bond of p-nitrophenyl esters. EstU1 assumes a ß-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 ß-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 ß-lactam antibiotics. This result explains the weak ß-lactamase activity of EstU1 compared with class C ß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Lactamases
/
Carboxylesterase
Language:
En
Journal:
Proteins
Journal subject:
BIOQUIMICA
Year:
2013
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA