Matches in SemOpenAlex for { <https://semopenalex.org/work/W3122000208> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W3122000208 abstract "Increased calpain activity is linked to neuroinflammation including a heritable retinal disease caused by hyper-activating mutations in the calcium-activated calpain-5 (CAPN5) protease. Although structures for classical calpains have been described, the structure of CAPN5, a non-classical calpain, remains undetermined. Herein, we report the 2.8 A crystal structure of the human CAPN5 protease core (CAPN5-PC). Compared to classical calpains, CAPN5-PC requires high Ca2+ concentrations for maximal activity. Structure-based phylogenetic analysis revealed that CAPN5-PC contains three elongated flexible loops compared to its classical counterparts. The presence of a disease-causing mutation (c.799G>A, p.Gly267Ser) on the unique C2 loop revealed a novel function for this region in regulating enzymatic activity. This mechanism could be transferred to distant calpains, using synthetic calpain hybrids, suggesting an evolutionary mechanism for fine-tuning calpain function by modifying flexible loops. Further, the open (inactive) conformation of the CAPN5-PC structure provides an opportunity for identifying inhibitors that bind to CAPN5-specific residues and lock it in the inactivated form." @default.
- W3122000208 created "2021-02-01" @default.
- W3122000208 creator A5003705103 @default.
- W3122000208 creator A5008872960 @default.
- W3122000208 creator A5012657407 @default.
- W3122000208 creator A5036867048 @default.
- W3122000208 creator A5043378745 @default.
- W3122000208 creator A5046326117 @default.
- W3122000208 creator A5053933172 @default.
- W3122000208 creator A5070322421 @default.
- W3122000208 creator A5071470775 @default.
- W3122000208 creator A5074679766 @default.
- W3122000208 creator A5089206065 @default.
- W3122000208 date "2019-01-01" @default.
- W3122000208 modified "2023-10-16" @default.
- W3122000208 title "Structural Insights into the Unique Activation Mechanisms of a Non-Classical Calpain and its Disease-Causing Variants" @default.
- W3122000208 doi "https://doi.org/10.2139/ssrn.3469831" @default.
- W3122000208 hasPublicationYear "2019" @default.
- W3122000208 type Work @default.
- W3122000208 sameAs 3122000208 @default.
- W3122000208 citedByCount "0" @default.
- W3122000208 crossrefType "journal-article" @default.
- W3122000208 hasAuthorship W3122000208A5003705103 @default.
- W3122000208 hasAuthorship W3122000208A5008872960 @default.
- W3122000208 hasAuthorship W3122000208A5012657407 @default.
- W3122000208 hasAuthorship W3122000208A5036867048 @default.
- W3122000208 hasAuthorship W3122000208A5043378745 @default.
- W3122000208 hasAuthorship W3122000208A5046326117 @default.
- W3122000208 hasAuthorship W3122000208A5053933172 @default.
- W3122000208 hasAuthorship W3122000208A5070322421 @default.
- W3122000208 hasAuthorship W3122000208A5071470775 @default.
- W3122000208 hasAuthorship W3122000208A5074679766 @default.
- W3122000208 hasAuthorship W3122000208A5089206065 @default.
- W3122000208 hasConcept C104317684 @default.
- W3122000208 hasConcept C12554922 @default.
- W3122000208 hasConcept C181199279 @default.
- W3122000208 hasConcept C185592680 @default.
- W3122000208 hasConcept C2776714187 @default.
- W3122000208 hasConcept C501734568 @default.
- W3122000208 hasConcept C55493867 @default.
- W3122000208 hasConcept C56928146 @default.
- W3122000208 hasConcept C86803240 @default.
- W3122000208 hasConcept C95444343 @default.
- W3122000208 hasConceptScore W3122000208C104317684 @default.
- W3122000208 hasConceptScore W3122000208C12554922 @default.
- W3122000208 hasConceptScore W3122000208C181199279 @default.
- W3122000208 hasConceptScore W3122000208C185592680 @default.
- W3122000208 hasConceptScore W3122000208C2776714187 @default.
- W3122000208 hasConceptScore W3122000208C501734568 @default.
- W3122000208 hasConceptScore W3122000208C55493867 @default.
- W3122000208 hasConceptScore W3122000208C56928146 @default.
- W3122000208 hasConceptScore W3122000208C86803240 @default.
- W3122000208 hasConceptScore W3122000208C95444343 @default.
- W3122000208 hasLocation W31220002081 @default.
- W3122000208 hasOpenAccess W3122000208 @default.
- W3122000208 hasPrimaryLocation W31220002081 @default.
- W3122000208 hasRelatedWork W1600728970 @default.
- W3122000208 hasRelatedWork W2018578690 @default.
- W3122000208 hasRelatedWork W2021772242 @default.
- W3122000208 hasRelatedWork W2034762662 @default.
- W3122000208 hasRelatedWork W2057563075 @default.
- W3122000208 hasRelatedWork W2068429423 @default.
- W3122000208 hasRelatedWork W2070605833 @default.
- W3122000208 hasRelatedWork W2089838266 @default.
- W3122000208 hasRelatedWork W2314024519 @default.
- W3122000208 hasRelatedWork W3044029748 @default.
- W3122000208 isParatext "false" @default.
- W3122000208 isRetracted "false" @default.
- W3122000208 magId "3122000208" @default.
- W3122000208 workType "article" @default.