FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1988631963> ?p ?o ?g. }

• W1988631963 endingPage "4998" @default.
• W1988631963 startingPage "4990" @default.
• W1988631963 abstract "Pneumocystis jirovecii is an opportunistic pathogen that causes serious pneumonia in immunosuppressed patients. Standard therapy and prophylaxis include trimethoprim (TMP)-sulfamethoxazole; trimethoprim in this combination targets dihydrofolate reductase (DHFR). Fourteen clinically observed variants of P. jirovecii DHFR were produced recombinantly to allow exploration of the causes of clinically observed failure of therapy and prophylaxis that includes trimethoprim. Six DHFR variants (S31F, F36C, L65P, A67V, V79I, and I158V) showed resistance to inhibition by trimethoprim, with Ki values for trimethoprim 4-fold to 100-fold higher than those for the wild-type P. jirovecii DHFR. An experimental antifolate with more conformational flexibility than trimethoprim showed strong activity against one trimethoprim-resistant variant. The two variants that were most resistant to trimethoprim (F36C and L65P) also had increased Km values for dihydrofolic acid (DHFA). The catalytic rate constant (kcat) was unchanged for most variant forms of P. jirovecii DHFR but was significantly lowered in F36C protein; one naturally occurring variant with two amino acid substitutions (S106P and E127G) showed a doubling of kcat, as well as a Km for NADPH half that of the wild type. The strongest resistance to trimethoprim occurred with amino acid changes in the binding pocket for DHFA or trimethoprim, and the strongest effect on binding of NADPH was linked to a mutation involved in binding the phosphate group of the cofactor. This study marks the first confirmation that naturally occurring mutations in the gene for DHFR from P. jirovecii produce variant forms of DHFR that are resistant to trimethoprim and may contribute to clinically observed failures of standard therapy or prophylaxis." @default.
• W1988631963 created "2016-06-24" @default.
• W1988631963 creator A5024494412 @default.
• W1988631963 creator A5027119527 @default.
• W1988631963 creator A5052708209 @default.
• W1988631963 creator A5071627490 @default.
• W1988631963 creator A5088782676 @default.
• W1988631963 date "2013-10-01" @default.
• W1988631963 modified "2023-10-14" @default.
• W1988631963 title "Trimethoprim Resistance of Dihydrofolate Reductase Variants from Clinical Isolates of Pneumocystis jirovecii" @default.
• W1988631963 cites W1515673187 @default.
• W1988631963 cites W1970696486 @default.
• W1988631963 cites W1992138599 @default.
• W1988631963 cites W1997907868 @default.
• W1988631963 cites W2022779349 @default.
• W1988631963 cites W2059614919 @default.
• W1988631963 cites W2060463809 @default.
• W1988631963 cites W2062407667 @default.
• W1988631963 cites W2076206735 @default.
• W1988631963 cites W2091632754 @default.
• W1988631963 cites W2091738589 @default.
• W1988631963 cites W2096261579 @default.
• W1988631963 cites W2096717755 @default.
• W1988631963 cites W2099605180 @default.
• W1988631963 cites W2101386304 @default.
• W1988631963 cites W2123041977 @default.
• W1988631963 cites W2141501125 @default.
• W1988631963 cites W2145469243 @default.
• W1988631963 cites W2149868870 @default.
• W1988631963 cites W2160343648 @default.
• W1988631963 cites W2162003092 @default.
• W1988631963 cites W2168193353 @default.
• W1988631963 cites W2169849786 @default.
• W1988631963 doi "https://doi.org/10.1128/aac.01161-13" @default.
• W1988631963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3811448" @default.
• W1988631963 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23896474" @default.
• W1988631963 hasPublicationYear "2013" @default.
• W1988631963 type Work @default.
• W1988631963 sameAs 1988631963 @default.
• W1988631963 citedByCount "39" @default.
• W1988631963 countsByYear W19886319632015 @default.
• W1988631963 countsByYear W19886319632016 @default.
• W1988631963 countsByYear W19886319632017 @default.
• W1988631963 countsByYear W19886319632018 @default.
• W1988631963 countsByYear W19886319632019 @default.
• W1988631963 countsByYear W19886319632020 @default.
• W1988631963 countsByYear W19886319632021 @default.
• W1988631963 countsByYear W19886319632022 @default.
• W1988631963 countsByYear W19886319632023 @default.
• W1988631963 crossrefType "journal-article" @default.
• W1988631963 hasAuthorship W1988631963A5024494412 @default.
• W1988631963 hasAuthorship W1988631963A5027119527 @default.
• W1988631963 hasAuthorship W1988631963A5052708209 @default.
• W1988631963 hasAuthorship W1988631963A5071627490 @default.
• W1988631963 hasAuthorship W1988631963A5088782676 @default.
• W1988631963 hasBestOaLocation W19886319631 @default.
• W1988631963 hasConcept C159047783 @default.
• W1988631963 hasConcept C181199279 @default.
• W1988631963 hasConcept C2776694085 @default.
• W1988631963 hasConcept C2777559004 @default.
• W1988631963 hasConcept C2778397455 @default.
• W1988631963 hasConcept C2779425571 @default.
• W1988631963 hasConcept C2780728791 @default.
• W1988631963 hasConcept C2781320022 @default.
• W1988631963 hasConcept C2781382166 @default.
• W1988631963 hasConcept C3013748606 @default.
• W1988631963 hasConcept C501593827 @default.
• W1988631963 hasConcept C54355233 @default.
• W1988631963 hasConcept C55493867 @default.
• W1988631963 hasConcept C86803240 @default.
• W1988631963 hasConcept C89423630 @default.
• W1988631963 hasConceptScore W1988631963C159047783 @default.
• W1988631963 hasConceptScore W1988631963C181199279 @default.
• W1988631963 hasConceptScore W1988631963C2776694085 @default.
• W1988631963 hasConceptScore W1988631963C2777559004 @default.
• W1988631963 hasConceptScore W1988631963C2778397455 @default.
• W1988631963 hasConceptScore W1988631963C2779425571 @default.
• W1988631963 hasConceptScore W1988631963C2780728791 @default.
• W1988631963 hasConceptScore W1988631963C2781320022 @default.
• W1988631963 hasConceptScore W1988631963C2781382166 @default.
• W1988631963 hasConceptScore W1988631963C3013748606 @default.
• W1988631963 hasConceptScore W1988631963C501593827 @default.
• W1988631963 hasConceptScore W1988631963C54355233 @default.
• W1988631963 hasConceptScore W1988631963C55493867 @default.
• W1988631963 hasConceptScore W1988631963C86803240 @default.
• W1988631963 hasConceptScore W1988631963C89423630 @default.
• W1988631963 hasIssue "10" @default.
• W1988631963 hasLocation W19886319631 @default.
• W1988631963 hasLocation W19886319632 @default.
• W1988631963 hasLocation W19886319633 @default.
• W1988631963 hasLocation W19886319634 @default.
• W1988631963 hasOpenAccess W1988631963 @default.
• W1988631963 hasPrimaryLocation W19886319631 @default.
• W1988631963 hasRelatedWork W1760004350 @default.
• W1988631963 hasRelatedWork W1988631963 @default.
• W1988631963 hasRelatedWork W1994670783 @default.
• W1988631963 hasRelatedWork W2003703135 @default.
• W1988631963 hasRelatedWork W2038277928 @default.

• next