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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1997-6-19
|
| pubmed:databankReference | |
| pubmed:abstractText |
The gene encoding the dihydropteroate synthase of staphylococcus aureus has been cloned, sequenced and expressed in Escherichia coli. The protein has been purified for biochemical characterization and X-ray crystallographic studies. The enzyme is a dimer in solution, has a steady state kinetic mechanism that suggests random binding of the two substrates and half-site reactivity. The crystal structure of apo-enzyme and a binary complex with the substrate analogue hydroxymethylpterin pyrophosphate were determined at 2.2 A and 2.4 A resolution, respectively. The enzyme belongs to the group of "TIM-barrel" proteins and crystallizes as a non-crystallographic dimer. Only one molecule of the substrate analogue bound per dimer in the crystal. Sequencing of nine sulfonamide-resistant clinical isolates has shown that as many as 14 residues could be involved in resistance development. The residues are distributed over the surface of the protein, which defies a simple interpretation of their roles in resistance. Nevertheless, the three-dimensional structure of the substrate analogue binary complex could give important insight into the molecular mechanism of this enzyme.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0022-2836
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
25
|
| pubmed:volume |
268
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
21-30
|
| pubmed:dateRevised |
2003-7-14
|
| pubmed:meshHeading |
pubmed-meshheading:9149138-Amino Acid Sequence,
pubmed-meshheading:9149138-Binding Sites,
pubmed-meshheading:9149138-Cloning, Molecular,
pubmed-meshheading:9149138-Crystallography, X-Ray,
pubmed-meshheading:9149138-Dihydropteroate Synthase,
pubmed-meshheading:9149138-Drug Resistance, Microbial,
pubmed-meshheading:9149138-Escherichia coli,
pubmed-meshheading:9149138-Kinetics,
pubmed-meshheading:9149138-Microbial Sensitivity Tests,
pubmed-meshheading:9149138-Models, Molecular,
pubmed-meshheading:9149138-Molecular Sequence Data,
pubmed-meshheading:9149138-Mutation,
pubmed-meshheading:9149138-Polymerase Chain Reaction,
pubmed-meshheading:9149138-Protein Conformation,
pubmed-meshheading:9149138-Recombinant Proteins,
pubmed-meshheading:9149138-Sequence Homology, Amino Acid,
pubmed-meshheading:9149138-Staphylococcus aureus,
pubmed-meshheading:9149138-Sulfamethoxazole,
pubmed-meshheading:9149138-Sulfonamides
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Structure and function of the dihydropteroate synthase from Staphylococcus aureus.
|
| pubmed:affiliation |
F. Hoffmann-La Roche Ltd, Pharma Preclinical Research Department, Basel, Switzerland.
|
| pubmed:publicationType |
Journal Article
|