FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1996803443> ?p ?o ?g. }

• W1996803443 endingPage "3350" @default.
• W1996803443 startingPage "3337" @default.
• W1996803443 abstract "The role of individual intracellular (IC) loops linking transmembrane (TM) domains in P-glycoprotein (P-gp) function remains largely unknown. The high degree of sequence conservation of these regions in the P-gp family and other ABC transporters suggests an important role in a common mechanism of action of these proteins. To gain insight into this problem, we have randomly mutagenized a portion of TM2, the entire IC1 loop, TM3, the entire extracellular loop (EC2), and part of TM4, and analyzed the effect of such mutations on P-gp function. Random mutagenesis was carried out using Taq DNA polymerase and dITP under conditions of low polymerase fidelity, and the mutagenized segments were reintroduced in the full length mdr3 cDNA by homologous recombination in the yeast Saccharomyces cerevisiae strain JPY201. The biological activity of mutant P-gp variants was analyzed in yeast by their ability to confer cellular resistance to the antifungal drug FK506 and the peptide ionophore valinomycin, and by their ability to complement the yeast Ste6 gene and restore mating in a yeast strain bearing a null mutation [Raymond, M., et al. (1992) Science 256, 232−4] at this locus. The analysis of 782 independent yeast transformants allowed the identification of 49 independent mutants bearing single amino acid substitutions in the mutagenized segment resulting in an altered P-gp function. The mutants could be phenotypically classified into two major groups, those that resulted in partial or complete overall loss of function and those that seemed to affect substrate specificity. Several of the mutants affecting overall activity mapped in IC1; in particular we identified a segment of four consecutive mutation sensitive residues (TRLT, positions 169−172) with such a phenotype. On the other hand, we identified a cluster of mutants affecting substrate specificity within the short EC2 segment and in the adjacent portion of the neighboring TM4 domain. Expression and partial purification of a representative subset of these mutants showed that in all but two cases, loss of function was associated with loss of drug-induced ATPase activity of P-gp. Therefore, it appears that TM domains, IC and EC loops, are structurally and functionally tightly coupled in the process of drug stimulatable ATPase characteristic of P-gp." @default.
• W1996803443 created "2016-06-24" @default.
• W1996803443 creator A5037048441 @default.
• W1996803443 creator A5045348393 @default.
• W1996803443 date "1998-02-18" @default.
• W1996803443 modified "2023-09-27" @default.
• W1996803443 title "Mutational Analysis of the P-Glycoprotein First Intracellular Loop and Flanking Transmembrane Domains" @default.
• W1996803443 cites W1499612376 @default.
• W1996803443 cites W1503660683 @default.
• W1996803443 cites W1503872106 @default.
• W1996803443 cites W1513685218 @default.
• W1996803443 cites W1530840777 @default.
• W1996803443 cites W1558851509 @default.
• W1996803443 cites W1591356314 @default.
• W1996803443 cites W1594196316 @default.
• W1996803443 cites W1598654033 @default.
• W1996803443 cites W1984555522 @default.
• W1996803443 cites W1989544135 @default.
• W1996803443 cites W2011163178 @default.
• W1996803443 cites W2026968208 @default.
• W1996803443 cites W2039599894 @default.
• W1996803443 cites W2048408401 @default.
• W1996803443 cites W2060914976 @default.
• W1996803443 cites W2072412837 @default.
• W1996803443 cites W2112001901 @default.
• W1996803443 doi "https://doi.org/10.1021/bi972680x" @default.
• W1996803443 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9521654" @default.
• W1996803443 hasPublicationYear "1998" @default.
• W1996803443 type Work @default.
• W1996803443 sameAs 1996803443 @default.
• W1996803443 citedByCount "45" @default.
• W1996803443 countsByYear W19968034432012 @default.
• W1996803443 countsByYear W19968034432014 @default.
• W1996803443 countsByYear W19968034432015 @default.
• W1996803443 countsByYear W19968034432017 @default.
• W1996803443 countsByYear W19968034432020 @default.
• W1996803443 countsByYear W19968034432022 @default.
• W1996803443 countsByYear W19968034432023 @default.
• W1996803443 crossrefType "journal-article" @default.
• W1996803443 hasAuthorship W1996803443A5037048441 @default.
• W1996803443 hasAuthorship W1996803443A5045348393 @default.
• W1996803443 hasConcept C104317684 @default.
• W1996803443 hasConcept C118892022 @default.
• W1996803443 hasConcept C143065580 @default.
• W1996803443 hasConcept C153911025 @default.
• W1996803443 hasConcept C16318435 @default.
• W1996803443 hasConcept C170493617 @default.
• W1996803443 hasConcept C24530287 @default.
• W1996803443 hasConcept C2777576037 @default.
• W1996803443 hasConcept C2779222958 @default.
• W1996803443 hasConcept C54355233 @default.
• W1996803443 hasConcept C55493867 @default.
• W1996803443 hasConcept C86803240 @default.
• W1996803443 hasConceptScore W1996803443C104317684 @default.
• W1996803443 hasConceptScore W1996803443C118892022 @default.
• W1996803443 hasConceptScore W1996803443C143065580 @default.
• W1996803443 hasConceptScore W1996803443C153911025 @default.
• W1996803443 hasConceptScore W1996803443C16318435 @default.
• W1996803443 hasConceptScore W1996803443C170493617 @default.
• W1996803443 hasConceptScore W1996803443C24530287 @default.
• W1996803443 hasConceptScore W1996803443C2777576037 @default.
• W1996803443 hasConceptScore W1996803443C2779222958 @default.
• W1996803443 hasConceptScore W1996803443C54355233 @default.
• W1996803443 hasConceptScore W1996803443C55493867 @default.
• W1996803443 hasConceptScore W1996803443C86803240 @default.
• W1996803443 hasIssue "10" @default.
• W1996803443 hasLocation W19968034431 @default.
• W1996803443 hasLocation W19968034432 @default.
• W1996803443 hasOpenAccess W1996803443 @default.
• W1996803443 hasPrimaryLocation W19968034431 @default.
• W1996803443 hasRelatedWork W188926022 @default.
• W1996803443 hasRelatedWork W1917314105 @default.
• W1996803443 hasRelatedWork W2062385823 @default.
• W1996803443 hasRelatedWork W2072731694 @default.
• W1996803443 hasRelatedWork W2094041192 @default.
• W1996803443 hasRelatedWork W2133882122 @default.
• W1996803443 hasRelatedWork W2225940343 @default.
• W1996803443 hasRelatedWork W2391501070 @default.
• W1996803443 hasRelatedWork W3120238434 @default.
• W1996803443 hasRelatedWork W4247688091 @default.
• W1996803443 hasVolume "37" @default.
• W1996803443 isParatext "false" @default.
• W1996803443 isRetracted "false" @default.
• W1996803443 magId "1996803443" @default.
• W1996803443 workType "article" @default.