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http://purl.uniprot.org/citations/11013231http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11013231http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11013231http://www.w3.org/2000/01/rdf-schema#comment"Pneumocystis carinii remains a persistent cause of severe pneumonia in immune compromised patients. Recent studies indicate that P. carinii is a fungal species possessing a glucan-rich cyst wall. Pneumocandin antagonists of beta-1,3-glucan synthesis rapidly suppress infection in animal models of P. carinii pneumonia. We, therefore, sought to define the molecular mechanisms of beta-glucan cell wall assembly by P. carinii. Membrane extracts derived from freshly purified P. carinii incorporate uridine 5'-diphosphoglucose into insoluble carbohydrate, in a manner that was completely inhibited by the pneumocandin L733-560, an antagonist of Gsc-1-type beta-glucan synthetases. Using degenerative polymerase chain reaction and library screening, the P. carinii Gsc-1 catalytic subunit of beta-1,3-glucan synthetase was cloned and characterized. P. carinii gsc1 exhibited homology to phylogenetically related fungal beta-1,3-glucan synthetases, encoding a predicted 214-kDa integral membrane protein with 12 transmembrane domain structure. Immunoprecipitation of P. carinii extracts, with a synthetic peptide anti-Gsc-1 antibody, specifically yielded a protein of 219.4 kDa, which was also capable of incorporating 5'-diphosphoglucose into insoluble glucan carbohydrate. As opposed to other fungi, the expression of gsc-1 mRNA is uniquely regulated over P. carinii's life cycle, having minimal expression in trophic forms, but substantial expression in the thick-walled cystic form of the organism. These results indicate that P. carinii contains a unique catalytic subunit of beta-1,3-glucan synthetase utilized in cyst wall formation. Because synthesis of beta-1,3-glucan is absent in mammalian cells, inhibition of the P. carinii Gsc-1 represents an attractive molecular target for therapeutic exploitation."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.org/dc/terms/identifier"doi:10.1074/jbc.M002103200"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m002103200"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/author"Kottom T.J."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/author"Kottom T.J."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/author"Limper A.H."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/author"Limper A.H."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/pages"40628-40634"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/pages"40628-40634"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/title"Cell wall assembly by Pneumocystis carinii. Evidence for a unique gsc-1 subunit mediating beta -1,3-glucan deposition."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/title"Cell wall assembly by Pneumocystis carinii. Evidence for a unique gsc-1 subunit mediating beta -1,3-glucan deposition."xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/11013231http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/11013231http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11013231
http://purl.uniprot.org/citations/11013231http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11013231
http://purl.uniprot.org/citations/11013231http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11013231
http://purl.uniprot.org/citations/11013231http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11013231
http://purl.uniprot.org/uniprot/Q9HEZ4http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/11013231
http://purl.uniprot.org/uniprot/Q9UVL8http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/11013231