FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2010143253> ?p ?o ?g. }

• W2010143253 endingPage "175" @default.
• W2010143253 startingPage "167" @default.
• W2010143253 abstract "Cytochrome P450c17 catalyzes steroid 17α-hydroxylase and 17,20-lyase activities and hence is a key enzyme in the production of human glucocorticoids and sex steroids. These two activities are catalyzed in a single substrate-binding site but are regulated independently in human physiology. We have recently shown that cytochrome b5 facilitates 17,20-lyase activity by allosterically promoting the interaction of P450c17 with P450 oxidoreductase (OR) and that the human P450c17 mutations, R347H and R358Q, selectively destroy 17,20-lyase activity while sparing 17α-hydroxylase activity. We transfected COS-1 cells with vectors for these P450c17 mutants and found that an excess of OR and b5 restored a small amount of 17,20-lyase activity, suggesting the mutations interfere with electron donation. To determine whether these mutations selectively interfere with the interaction of P450c17 and its electron-donating system, we expressed each P450c17 mutant in yeast with or without OR, b5, or both, and measured enzyme kinetics in yeast microsomes using pregnenolone and 17α-hydroxypregnenolone as substrates. The apparent Michaelis-Menten (Km) values for the R347H mutant with and without coexpressed OR were 0.2 and 0.6 μm, respectively, and for the R358Q mutant with and without OR they were 0.3 and 0.4μ m, respectively; these values did not differ significantly from the wild-type values of 0.4 and 0.8μ m with and without OR, respectively. Furthermore, coincubation with 17α-hydroxypregnenolone showed a competitive mechanism for interference of catalysis. The similar kinetics and the competitive inhibition prove that the mutations did not affect the active site. Coexpression of the mutants with OR yielded insignificant 17,20-lyase activity, but addition of a 30:1 molar excess cytochrome b5 to these microsomes restored partial 17,20-lyase activity, with the R358Q mutant achieving twice the activity of the R347H mutant. These data indicate that both mutations selectively interfere with 17,20-lyase activity by altering the interaction of P450c17 with OR, thus proving that the lyase activity was disrupted by interfering with electron transfer. Furthermore, the data offer the first evidence that R347 is a crucial component of the site at which b5 interacts with the P450c17·OR complex to promote electron transfer." @default.
• W2010143253 created "2016-06-24" @default.
• W2010143253 creator A5055037280 @default.
• W2010143253 creator A5064575852 @default.
• W2010143253 creator A5068374034 @default.
• W2010143253 date "1999-01-01" @default.
• W2010143253 modified "2023-10-17" @default.
• W2010143253 title "P450c17 Mutations R347H and R358Q Selectively Disrupt 17,20-Lyase Activity by Disrupting Interactions with P450 Oxidoreductase and Cytochrome b₅" @default.
• W2010143253 cites W1515404266 @default.
• W2010143253 cites W1534713573 @default.
• W2010143253 cites W1551857288 @default.
• W2010143253 cites W1570978364 @default.
• W2010143253 cites W1951469402 @default.
• W2010143253 cites W1963545612 @default.
• W2010143253 cites W1974392518 @default.
• W2010143253 cites W1982956495 @default.
• W2010143253 cites W1994460876 @default.
• W2010143253 cites W1995802297 @default.
• W2010143253 cites W1999383531 @default.
• W2010143253 cites W2002730596 @default.
• W2010143253 cites W2007165067 @default.
• W2010143253 cites W2011610631 @default.
• W2010143253 cites W2019527863 @default.
• W2010143253 cites W2020881856 @default.
• W2010143253 cites W2022711133 @default.
• W2010143253 cites W2037405534 @default.
• W2010143253 cites W2041567083 @default.
• W2010143253 cites W2043757280 @default.
• W2010143253 cites W2053012453 @default.
• W2010143253 cites W2058350561 @default.
• W2010143253 cites W2059850722 @default.
• W2010143253 cites W2066600629 @default.
• W2010143253 cites W2086660631 @default.
• W2010143253 cites W2089972450 @default.
• W2010143253 cites W2095040842 @default.
• W2010143253 cites W2115296460 @default.
• W2010143253 cites W2126733133 @default.
• W2010143253 cites W2145261669 @default.
• W2010143253 cites W2147995093 @default.
• W2010143253 cites W2157020561 @default.
• W2010143253 cites W2164097694 @default.
• W2010143253 cites W2999510508 @default.
• W2010143253 doi "https://doi.org/10.1210/mend.13.1.0219" @default.
• W2010143253 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9892022" @default.
• W2010143253 hasPublicationYear "1999" @default.
• W2010143253 type Work @default.
• W2010143253 sameAs 2010143253 @default.
• W2010143253 citedByCount "147" @default.
• W2010143253 countsByYear W20101432532012 @default.
• W2010143253 countsByYear W20101432532013 @default.
• W2010143253 countsByYear W20101432532014 @default.
• W2010143253 countsByYear W20101432532015 @default.
• W2010143253 countsByYear W20101432532016 @default.
• W2010143253 countsByYear W20101432532017 @default.
• W2010143253 countsByYear W20101432532018 @default.
• W2010143253 countsByYear W20101432532019 @default.
• W2010143253 countsByYear W20101432532020 @default.
• W2010143253 countsByYear W20101432532021 @default.
• W2010143253 countsByYear W20101432532022 @default.
• W2010143253 countsByYear W20101432532023 @default.
• W2010143253 crossrefType "journal-article" @default.
• W2010143253 hasAuthorship W2010143253A5055037280 @default.
• W2010143253 hasAuthorship W2010143253A5064575852 @default.
• W2010143253 hasAuthorship W2010143253A5068374034 @default.
• W2010143253 hasBestOaLocation W20101432531 @default.
• W2010143253 hasConcept C104317684 @default.
• W2010143253 hasConcept C143065580 @default.
• W2010143253 hasConcept C153911025 @default.
• W2010143253 hasConcept C181199279 @default.
• W2010143253 hasConcept C2777269803 @default.
• W2010143253 hasConcept C2779222958 @default.
• W2010143253 hasConcept C2779268744 @default.
• W2010143253 hasConcept C2779384962 @default.
• W2010143253 hasConcept C2780193516 @default.
• W2010143253 hasConcept C2780768313 @default.
• W2010143253 hasConcept C2780902042 @default.
• W2010143253 hasConcept C526171541 @default.
• W2010143253 hasConcept C55493867 @default.
• W2010143253 hasConcept C71315377 @default.
• W2010143253 hasConcept C86803240 @default.
• W2010143253 hasConcept C87644729 @default.
• W2010143253 hasConceptScore W2010143253C104317684 @default.
• W2010143253 hasConceptScore W2010143253C143065580 @default.
• W2010143253 hasConceptScore W2010143253C153911025 @default.
• W2010143253 hasConceptScore W2010143253C181199279 @default.
• W2010143253 hasConceptScore W2010143253C2777269803 @default.
• W2010143253 hasConceptScore W2010143253C2779222958 @default.
• W2010143253 hasConceptScore W2010143253C2779268744 @default.
• W2010143253 hasConceptScore W2010143253C2779384962 @default.
• W2010143253 hasConceptScore W2010143253C2780193516 @default.
• W2010143253 hasConceptScore W2010143253C2780768313 @default.
• W2010143253 hasConceptScore W2010143253C2780902042 @default.
• W2010143253 hasConceptScore W2010143253C526171541 @default.
• W2010143253 hasConceptScore W2010143253C55493867 @default.
• W2010143253 hasConceptScore W2010143253C71315377 @default.
• W2010143253 hasConceptScore W2010143253C86803240 @default.
• W2010143253 hasConceptScore W2010143253C87644729 @default.
• W2010143253 hasIssue "1" @default.

• next