Linked Life Data

8429044

Source:http://linkedlifedata.com/resource/pubmed/id/8429044

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-3-9
pubmed:abstractText
A growing number of extended spectrum SHV-type beta-lactamases capable of hydrolyzing third-generation cephalosporins such as cefotaxime and ceftazidime have been reported. These new enzymes differ by a few amino acids from SHV-1, an enzyme incapable of hydrolyzing these drugs. Two of these substitutions, Gly-238-->Ser and Glu-240-->Lys, are in a key beta-strand of the catalytic site of class A beta-lactamases. To understand the structural basis of these new activities, we first subcloned the DNA region coding for SHV-1 and SHV-2 and did site-directed mutagenesis to create two mutant SHV-1 proteins containing Ser and Glu or Gly and Lys and two mutant SHV-2 proteins containing Gly and Glu or Ser and Lys in positions 238 and 240, respectively. Phenotypic analysis (antibiograms and minimum inhibitory concentrations) and activity spectra of mutant enzymes showed that Ser-238 is critical for cefotaxime hydrolysis whereas both Ser-238 and Lys-240 are needed for strong ceftazidime hydrolysis. A three-dimensional model for SHV beta-lactamase complexes was constructed using the crystallographic structure of the homologous Bacillus licheniformis beta-lactamase, the complex of cefotaxime with the Streptomyces sp. R61 D-alanyl-D-alanine peptidase, and the complex of aztreonam with the Citrobacter freundii beta-lactamase. The modeling of SHV beta-lactamase complexes showed that factors which are most likely to correlate with binding and kinetic data are the size of the relatively buried amino acid at position 238 and the electrostatic charge of the exposed group at position 240.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
268
pubmed:geneSymbol
bla
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3690-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8429044-Amino Acid Sequence, pubmed-meshheading:8429044-Bacillus, pubmed-meshheading:8429044-Base Sequence, pubmed-meshheading:8429044-Binding Sites, pubmed-meshheading:8429044-Cefotaxime, pubmed-meshheading:8429044-Ceftazidime, pubmed-meshheading:8429044-Cephalosporins, pubmed-meshheading:8429044-Citrobacter freundii, pubmed-meshheading:8429044-Hydrolysis, pubmed-meshheading:8429044-Lysine, pubmed-meshheading:8429044-Models, Molecular, pubmed-meshheading:8429044-Molecular Sequence Data, pubmed-meshheading:8429044-Molecular Structure, pubmed-meshheading:8429044-Mutagenesis, Site-Directed, pubmed-meshheading:8429044-Oligodeoxyribonucleotides, pubmed-meshheading:8429044-Protein Structure, Secondary, pubmed-meshheading:8429044-Recombinant Proteins, pubmed-meshheading:8429044-Serine, pubmed-meshheading:8429044-Streptomyces, pubmed-meshheading:8429044-beta-Lactamases
pubmed:year
1993
pubmed:articleTitle
Role of Ser-238 and Lys-240 in the hydrolysis of third-generation cephalosporins by SHV-type beta-lactamases probed by site-directed mutagenesis and three-dimensional modeling.
pubmed:affiliation
Département de Microbiologie, Faculté de Médecine, Université Laval, Ste-Foy, Québec, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't