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http://purl.uniprot.org/citations/9728538http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9728538http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9728538http://www.w3.org/2000/01/rdf-schema#comment"Multidrug-resistant Streptococcus pneumoniae strains have emerged over the past decade at an alarming rate. The molecular mechanism of trimethoprim resistance was investigated in 5 pneumococcal strains isolated in the Washington, DC, area from patients with invasive infections. Cloning and sequencing of the trimethoprim resistance determinant from these pneumococci indicated that an altered chromosome-encoded dihydrofolate reductase (DHFR) was responsible for the observed resistance. Comparison of DHFR sequences from pneumococcal strains with various susceptibilities to trimethoprim, together with site-directed mutagenesis, revealed that substitution of isoleucine-100 with a leucine residue resulted in trimethoprim resistance. Hydrogen bonding between the carbonyl oxygen of isoleucine-100 and the 4-amino group of trimethoprim is proposed to play a critical role in the inhibition of DHFR by trimethoprim. This enzyme-substrate model should facilitate the design of new antibacterial agents with improved activity against S. pneumoniae."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.org/dc/terms/identifier"doi:10.1086/515371"xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Pikis A."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Pikis A."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Keith J.M."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Keith J.M."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Rodriguez W.J."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Rodriguez W.J."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Donkersloot J.A."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/author"Donkersloot J.A."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/name"J. Infect. Dis."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/name"J Infect Dis"xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/pages"700-706"xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/pages"700-706"xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/title"A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/title"A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae."xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/volume"178"xsd:string
http://purl.uniprot.org/citations/9728538http://purl.uniprot.org/core/volume"178"xsd:string
http://purl.uniprot.org/citations/9728538http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9728538
http://purl.uniprot.org/citations/9728538http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9728538
http://purl.uniprot.org/citations/9728538http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/9728538