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Understanding the acylation mechanisms of active‐site serine penicillin‐recognizing proteins: A molecular dynamics simulation study
Author(s) -
Oliva Mónica,
Dideberg Otto,
Field Martin J.
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.10450
Subject(s) - penicillin binding proteins , enzyme , antibiotics , biochemistry , peptidoglycan , acylation , lipid ii , chemistry , serine , penicillin , active site , streptomyces , bacteria , microbiology and biotechnology , biology , genetics , catalysis
β‐Lactam antibiotics inhibit enzymes involved in the last step of peptidoglycan synthesis. These enzymes, also identified as penicillin‐binding proteins (PBPs), form a long‐lived acyl‐enzyme complex with β‐lactams. Antibiotic resistance is mainly due to the production of β‐lactamases, which are enzymes that hydrolyze the antibiotics and so prevent them reaching and inactivating their targets, and to mutations of the PBPs that decrease their affinity for the antibiotics. In this study, we present a theoretical study of several penicillin‐recognizing proteins complexed with various β‐lactam antibiotics. Hybrid quantum mechanical/molecular mechanical potentials in conjunction with molecular dynamics simulations have been performed to understand the role of several residues, and pK a calculations have also been done to determine their protonation state. We analyze the differences between the β‐lactamase TEM‐1, the membrane‐bound PBP2x of Streptococcus pneumoniae , and the soluble DD‐transpeptidase of Streptomyces K15 . Proteins 2003. © 2003 Wiley‐Liss, Inc.