FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2953624658> ?p ?o ?g. }

• W2953624658 endingPage "838" @default.
• W2953624658 startingPage "831" @default.
• W2953624658 abstract "Classical homocystinuria is a recessive inborn error of metabolism caused by mutations in the cystathionine beta-synthase (CBS) gene. The highest incidence of CBS deficiency in the world is found in the country of Qatar due to the combination of high rates of consanguinity and the presence of a founder mutation, c.1006C>T (p.R336C). This mutation does not respond to pyridoxine and is considered severe. Here we describe the creation of a mouse that is null for the mouse Cbs gene and expresses human p.R336C CBS from a zinc-inducible transgene (Tg-R336C Cbs -/- ). Zinc-treated Tg-R336C Cbs -/- mice have extreme elevation in both serum total homocysteine (tHcy) and liver tHcy compared with control transgenic mice. Both the steady-state protein levels and CBS enzyme activity levels in liver lysates from Tg-R336C Cbs -/- mice are significantly reduced compared to that found in Tg-hCBS Cbs -/- mice expressing wild-type human CBS. Treatment of Tg-R336C Cbs -/- mice with the proteasome inhibitor bortezomib results in stabilization of liver CBS protein and an increase in activity to levels found in corresponding Tg-hCBS Cbs -/- wild type mice. Surprisingly, serum tHcy did not fully correct even though liver enzyme activity was as high as control animals. This discrepancy is explained by in vitro enzymatic studies of mouse liver extracts showing that p.R336C causes reduced binding affinity for the substrate serine by almost 7-fold and significantly increased dependence on pyridoxal phosphate in the reaction buffer. These studies demonstrate that the p.R336C alteration effects both protein stability and substrate/cofactor binding." @default.
• W2953624658 created "2019-07-12" @default.
• W2953624658 creator A5011552984 @default.
• W2953624658 creator A5016520050 @default.
• W2953624658 creator A5038589006 @default.
• W2953624658 creator A5040633590 @default.
• W2953624658 creator A5043117402 @default.
• W2953624658 creator A5050151002 @default.
• W2953624658 creator A5051979437 @default.
• W2953624658 creator A5060448976 @default.
• W2953624658 creator A5076585377 @default.
• W2953624658 creator A5085513914 @default.
• W2953624658 creator A5086746753 @default.
• W2953624658 date "2019-07-10" @default.
• W2953624658 modified "2023-10-13" @default.
• W2953624658 title "Analysis of the Qatari R336C cystathionine β‐synthase protein in mice" @default.
• W2953624658 cites W1550936604 @default.
• W2953624658 cites W1974576562 @default.
• W2953624658 cites W1980331857 @default.
• W2953624658 cites W2011550644 @default.
• W2953624658 cites W2027396261 @default.
• W2953624658 cites W2036846090 @default.
• W2953624658 cites W2040414889 @default.
• W2953624658 cites W2041158069 @default.
• W2953624658 cites W2048472770 @default.
• W2953624658 cites W2054065770 @default.
• W2953624658 cites W2054847530 @default.
• W2953624658 cites W2076159058 @default.
• W2953624658 cites W2080044106 @default.
• W2953624658 cites W2088844687 @default.
• W2953624658 cites W2089398645 @default.
• W2953624658 cites W2094115156 @default.
• W2953624658 cites W2095602231 @default.
• W2953624658 cites W2107277218 @default.
• W2953624658 cites W2119141156 @default.
• W2953624658 cites W2133377749 @default.
• W2953624658 cites W2134655304 @default.
• W2953624658 cites W2138439179 @default.
• W2953624658 cites W2143438556 @default.
• W2953624658 cites W2153477671 @default.
• W2953624658 cites W2169044648 @default.
• W2953624658 cites W2192080449 @default.
• W2953624658 cites W2613816816 @default.
• W2953624658 cites W2614590942 @default.
• W2953624658 cites W2899833778 @default.
• W2953624658 doi "https://doi.org/10.1002/jimd.12140" @default.
• W2953624658 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7336392" @default.
• W2953624658 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31240737" @default.
• W2953624658 hasPublicationYear "2019" @default.
• W2953624658 type Work @default.
• W2953624658 sameAs 2953624658 @default.
• W2953624658 citedByCount "6" @default.
• W2953624658 countsByYear W29536246582020 @default.
• W2953624658 countsByYear W29536246582021 @default.
• W2953624658 countsByYear W29536246582022 @default.
• W2953624658 countsByYear W29536246582023 @default.
• W2953624658 crossrefType "journal-article" @default.
• W2953624658 hasAuthorship W2953624658A5011552984 @default.
• W2953624658 hasAuthorship W2953624658A5016520050 @default.
• W2953624658 hasAuthorship W2953624658A5038589006 @default.
• W2953624658 hasAuthorship W2953624658A5040633590 @default.
• W2953624658 hasAuthorship W2953624658A5043117402 @default.
• W2953624658 hasAuthorship W2953624658A5050151002 @default.
• W2953624658 hasAuthorship W2953624658A5051979437 @default.
• W2953624658 hasAuthorship W2953624658A5060448976 @default.
• W2953624658 hasAuthorship W2953624658A5076585377 @default.
• W2953624658 hasAuthorship W2953624658A5085513914 @default.
• W2953624658 hasAuthorship W2953624658A5086746753 @default.
• W2953624658 hasBestOaLocation W29536246582 @default.
• W2953624658 hasConcept C102230213 @default.
• W2953624658 hasConcept C104317684 @default.
• W2953624658 hasConcept C126322002 @default.
• W2953624658 hasConcept C134018914 @default.
• W2953624658 hasConcept C141035611 @default.
• W2953624658 hasConcept C153911025 @default.
• W2953624658 hasConcept C16525657 @default.
• W2953624658 hasConcept C181199279 @default.
• W2953624658 hasConcept C185592680 @default.
• W2953624658 hasConcept C2779201268 @default.
• W2953624658 hasConcept C2779375456 @default.
• W2953624658 hasConcept C2780912031 @default.
• W2953624658 hasConcept C515207424 @default.
• W2953624658 hasConcept C55493867 @default.
• W2953624658 hasConcept C71924100 @default.
• W2953624658 hasConcept C86803240 @default.
• W2953624658 hasConceptScore W2953624658C102230213 @default.
• W2953624658 hasConceptScore W2953624658C104317684 @default.
• W2953624658 hasConceptScore W2953624658C126322002 @default.
• W2953624658 hasConceptScore W2953624658C134018914 @default.
• W2953624658 hasConceptScore W2953624658C141035611 @default.
• W2953624658 hasConceptScore W2953624658C153911025 @default.
• W2953624658 hasConceptScore W2953624658C16525657 @default.
• W2953624658 hasConceptScore W2953624658C181199279 @default.
• W2953624658 hasConceptScore W2953624658C185592680 @default.
• W2953624658 hasConceptScore W2953624658C2779201268 @default.
• W2953624658 hasConceptScore W2953624658C2779375456 @default.
• W2953624658 hasConceptScore W2953624658C2780912031 @default.
• W2953624658 hasConceptScore W2953624658C515207424 @default.

• next