Linked Life Data

11591698

Source:http://linkedlifedata.com/resource/pubmed/id/11591698

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2001-12-3
pubmed:abstractText
Class C beta-lactamases are commonly encoded on the chromosome of Gram-negative bacterial species. Mutations leading to increased expression of these enzymes are a common cause of resistance to many cephalosporins including extended spectrum cephalosporins. Recent reports of plasmid- and integrin-encoded class C beta-lactamases are a cause for concern because these enzymes are likely to spread horizontally to susceptible strains. Because of their increasing clinical significance, it is critical to identify the determinants of catalysis and substrate specificity of these enzymes. For this purpose, the codons of a set of 21 amino acid residues that encompass the active site region of the P99 beta-lactamase were individually randomized to create libraries containing all possible amino acid substitutions. The amino acid sequence requirements for the hydrolysis of ceftazidime, an extended spectrum cephalosporin commonly used to treat serious infections, were determined by selecting resistant mutants from each of the 21 libraries. DNA sequencing identified the residue positions that are critical for ceftazidime hydrolysis. In addition, it was found that certain amino acid substitutions in the omega-loop region of the P99 enzyme result in increased ceftazidime hydrolysis suggesting the loop is an important determinant of substrate specificity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46568-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Amino acid sequence determinants of extended spectrum cephalosporin hydrolysis by the class C P99 beta-lactamase.
pubmed:affiliation
Structural and Computational Biology and Molecular Biophysics Program, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.