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Substrate binding to mononuclear metallo‐β‐lactamase from Bacillus cereus
Author(s) -
Dal Peraro Matteo,
Vila Alejandro J.,
Carloni Paolo
Publication year - 2003
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.10554
Subject(s) - bacillus cereus , substrate (aquarium) , chemistry , nucleophile , hydroxide , cefotaxime , zinc , active site , ring (chemistry) , stereochemistry , hydrogen bond , catalysis , binding site , enzyme , crystallography , cereus , biochemistry , inorganic chemistry , biology , bacteria , organic chemistry , molecule , ecology , genetics , antibiotics
Structure and dynamics of substrate binding (cefotaxime) to the catalytic pocket of the mononuclear zinc‐β‐lactamase from Bacillus cereus are investigated by molecular dynamics simulations. The calculations, which are based on the hydrogen‐bond pattern recently proposed by Dal Peraro et al. (J Biol Inorg Chem 2002; 7:704–712), are carried out for both the free and the complexed enzyme. In the resting state, active site pattern and temperature B‐factors are in agreement with crystallographic data. In the complexed form, cefotaxime is accommodated into a stable orientation in the catalytic pocket within the nanosecond timescale, interacting with the enzyme zinc‐bound hydroxide and the surrounding loops. The β‐lactam ring remains stable and very close to the hydroxide nucleophile agent, giving a stable representation of the productive enzyme‐substrate complex. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.