Linked Life Data

11553637

Source:http://linkedlifedata.com/resource/pubmed/id/11553637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2001-11-23
pubmed:databankReference
pubmed:abstractText
Penicillin-binding proteins (PBPs) are the main targets for beta-lactam antibiotics, such as penicillins and cephalosporins, in a wide range of bacterial species. In some Gram-positive strains, the surge of resistance to treatment with beta-lactams is primarily the result of the proliferation of mosaic PBP-encoding genes, which encode novel proteins by recombination. PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and its modification is an essential step in the development of high level beta-lactam resistance. To understand such a resistance mechanism at an atomic level, we have solved the x-ray crystal structure of PBP2x from a highly penicillin-resistant clinical isolate of S. pneumoniae, Sp328, which harbors 83 mutations in the soluble region. In the proximity of the Sp328 PBP2x* active site, the Thr(338) --> Ala mutation weakens the local hydrogen bonding network, thus abrogating the stabilization of a crucial buried water molecule. In addition, the Ser(389) --> Leu and Asn(514) --> His mutations produce a destabilizing effect that generates an "open" active site. It has been suggested that peptidoglycan substrates for beta-lactam-resistant PBPs contain a large amount of abnormal, branched peptides, whereas sensitive strains tend to catalyze cross-linking of linear forms. Thus, in vivo, an "open" active site could facilitate the recognition of distinct, branched physiological substrates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45106-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11553637-Alanine, pubmed-meshheading:11553637-Amino Acid Sequence, pubmed-meshheading:11553637-Anti-Bacterial Agents, pubmed-meshheading:11553637-Asparagine, pubmed-meshheading:11553637-Binding Sites, pubmed-meshheading:11553637-Carrier Proteins, pubmed-meshheading:11553637-Crystallography, X-Ray, pubmed-meshheading:11553637-Drug Resistance, pubmed-meshheading:11553637-Leucine, pubmed-meshheading:11553637-Models, Molecular, pubmed-meshheading:11553637-Molecular Sequence Data, pubmed-meshheading:11553637-Mutagenesis, Site-Directed, pubmed-meshheading:11553637-Mutation, pubmed-meshheading:11553637-Penicillin-Binding Proteins, pubmed-meshheading:11553637-Penicillins, pubmed-meshheading:11553637-Protein Binding, pubmed-meshheading:11553637-Protein Conformation, pubmed-meshheading:11553637-Streptococcus pneumoniae, pubmed-meshheading:11553637-Threonine
pubmed:year
2001
pubmed:articleTitle
Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations.
pubmed:affiliation
Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale Jean-Pierre Ebel (CNRS/Commissariat à l'Energie Atomique), 41, rue Jules Horowitz, 38027 Grenoble, France. dessen@ibs.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't