FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2040755061> ?p ?o ?g. }

• W2040755061 endingPage "392" @default.
• W2040755061 startingPage "383" @default.
• W2040755061 abstract "Human 3α-hydroxysteroid dehydrogenases (HSDs) are potential drug targets since they regulate the occupancy and trans-activation of steroid hormone receptors by interconverting potent hormones with their cognate inactive metabolites. The human isoforms (AKR1C1-4) are all members of the aldo–keto reductase superfamily and display distinctive differences in steroid specificity and catalytic efficiency when compared with the closely related and more extensively studied rat 3α-HSD (AKR1C9). Specifically, AKR1C1-4 display 3α-, 17β- and 20α-HSD activities to varying degrees whereas AKR1C9 is positional- and stereo-specific for the 3α-HSD reaction. In addition, AKR1C1-4 isoforms have significantly lower catalytic efficiencies (kcat/Km) than AKR1C9 and this is largely due to a lower kcat. To understand these functional differences, human type 3 3α-HSD (AKR1C2) was studied as a representative human 3α-HSD. Comparison of the crystal structure of AKR1C2–NADP+–ursodeoxycholate ternary complex (3.0 Å) with that of the AKR1C9–NADP+–testosterone ternary complex (2.8 Å) demonstrates the expected conservancy in overall structure and active site topology. More interestingly, it reveals striking differences in the structure of the steroid binding pockets of the two enzymes and shows how ursodeoxycholate binds ‘backwards’ and ‘upside-down’ with respect to testosterone. This difference in steroid binding provides a structural basis for the broad positional specificity of AKR1C2 and the exquisite stereospecificity of AKR1C9. To determine why AKR1C2 has a much lower kcat than AKR1C9, the events associated with the binding of cofactor to both enzymes were studied by steady state fluorescence titration and stopped-flow experiments. Comparable Kd values for E–NADP(H) and kobs values for the fluorescence transients were obtained for the two enzymes. These data are consistent with both enzymes binding NADP(H) in a conserved manner which is supported by the available crystal structures. The results suggest that cofactor binding or release for the human and rat 3α-HSDs are similar and do not account for the observed differences in kcat. (Supported by DK40715 and CA90744 to T.M.P.)" @default.
• W2040755061 created "2016-06-24" @default.
• W2040755061 creator A5019174025 @default.
• W2040755061 creator A5037489740 @default.
• W2040755061 creator A5059737908 @default.
• W2040755061 date "2003-02-01" @default.
• W2040755061 modified "2023-09-23" @default.
• W2040755061 title "Examination of the differences in structure–function of human and rat 3α-hydroxysteroid dehydrogenase" @default.
• W2040755061 cites W1501373755 @default.
• W2040755061 cites W1512075851 @default.
• W2040755061 cites W1521225971 @default.
• W2040755061 cites W1581592573 @default.
• W2040755061 cites W1598526550 @default.
• W2040755061 cites W1770562442 @default.
• W2040755061 cites W1889970588 @default.
• W2040755061 cites W1978718013 @default.
• W2040755061 cites W1984253132 @default.
• W2040755061 cites W2006384462 @default.
• W2040755061 cites W2011478728 @default.
• W2040755061 cites W2014261005 @default.
• W2040755061 cites W2028325373 @default.
• W2040755061 cites W2032925662 @default.
• W2040755061 cites W2038241006 @default.
• W2040755061 cites W2045439485 @default.
• W2040755061 cites W2062949189 @default.
• W2040755061 cites W2104883596 @default.
• W2040755061 cites W2109886704 @default.
• W2040755061 cites W2131723216 @default.
• W2040755061 cites W2396256496 @default.
• W2040755061 cites W2396439345 @default.
• W2040755061 cites W2401471962 @default.
• W2040755061 cites W4205877643 @default.
• W2040755061 cites W72293034 @default.
• W2040755061 doi "https://doi.org/10.1016/s0009-2797(02)00207-7" @default.
• W2040755061 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12604225" @default.
• W2040755061 hasPublicationYear "2003" @default.
• W2040755061 type Work @default.
• W2040755061 sameAs 2040755061 @default.
• W2040755061 citedByCount "3" @default.
• W2040755061 countsByYear W20407550612013 @default.
• W2040755061 crossrefType "journal-article" @default.
• W2040755061 hasAuthorship W2040755061A5019174025 @default.
• W2040755061 hasAuthorship W2040755061A5037489740 @default.
• W2040755061 hasAuthorship W2040755061A5059737908 @default.
• W2040755061 hasConcept C104317684 @default.
• W2040755061 hasConcept C107824862 @default.
• W2040755061 hasConcept C119795356 @default.
• W2040755061 hasConcept C134651460 @default.
• W2040755061 hasConcept C170493617 @default.
• W2040755061 hasConcept C181199279 @default.
• W2040755061 hasConcept C185592680 @default.
• W2040755061 hasConcept C197957613 @default.
• W2040755061 hasConcept C2776317432 @default.
• W2040755061 hasConcept C2777486698 @default.
• W2040755061 hasConcept C2779268744 @default.
• W2040755061 hasConcept C2780902042 @default.
• W2040755061 hasConcept C2781067048 @default.
• W2040755061 hasConcept C2908857472 @default.
• W2040755061 hasConcept C41183919 @default.
• W2040755061 hasConcept C53345823 @default.
• W2040755061 hasConcept C55493867 @default.
• W2040755061 hasConcept C56856141 @default.
• W2040755061 hasConcept C71240020 @default.
• W2040755061 hasConcept C71315377 @default.
• W2040755061 hasConcept C86756495 @default.
• W2040755061 hasConcept C86803240 @default.
• W2040755061 hasConceptScore W2040755061C104317684 @default.
• W2040755061 hasConceptScore W2040755061C107824862 @default.
• W2040755061 hasConceptScore W2040755061C119795356 @default.
• W2040755061 hasConceptScore W2040755061C134651460 @default.
• W2040755061 hasConceptScore W2040755061C170493617 @default.
• W2040755061 hasConceptScore W2040755061C181199279 @default.
• W2040755061 hasConceptScore W2040755061C185592680 @default.
• W2040755061 hasConceptScore W2040755061C197957613 @default.
• W2040755061 hasConceptScore W2040755061C2776317432 @default.
• W2040755061 hasConceptScore W2040755061C2777486698 @default.
• W2040755061 hasConceptScore W2040755061C2779268744 @default.
• W2040755061 hasConceptScore W2040755061C2780902042 @default.
• W2040755061 hasConceptScore W2040755061C2781067048 @default.
• W2040755061 hasConceptScore W2040755061C2908857472 @default.
• W2040755061 hasConceptScore W2040755061C41183919 @default.
• W2040755061 hasConceptScore W2040755061C53345823 @default.
• W2040755061 hasConceptScore W2040755061C55493867 @default.
• W2040755061 hasConceptScore W2040755061C56856141 @default.
• W2040755061 hasConceptScore W2040755061C71240020 @default.
• W2040755061 hasConceptScore W2040755061C71315377 @default.
• W2040755061 hasConceptScore W2040755061C86756495 @default.
• W2040755061 hasConceptScore W2040755061C86803240 @default.
• W2040755061 hasLocation W20407550611 @default.
• W2040755061 hasLocation W20407550612 @default.
• W2040755061 hasOpenAccess W2040755061 @default.
• W2040755061 hasPrimaryLocation W20407550611 @default.
• W2040755061 hasRelatedWork W1770562442 @default.
• W2040755061 hasRelatedWork W1971297974 @default.
• W2040755061 hasRelatedWork W2030824583 @default.
• W2040755061 hasRelatedWork W2040755061 @default.
• W2040755061 hasRelatedWork W2074914199 @default.
• W2040755061 hasRelatedWork W2083360052 @default.

• next