FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2160168027> ?p ?o ?g. }

• W2160168027 endingPage "40877" @default.
• W2160168027 startingPage "40867" @default.
• W2160168027 abstract "Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine sulfamate analogue that was identified as a selective, mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a novel mechanism termed substrate-assisted inhibition (Brownell, J. E., Sintchak, M. D., Gavin, J. M., Liao, H., Bruzzese, F. J., Bump, N. J., Soucy, T. A., Milhollen, M. A., Yang, X., Burkhardt, A. L., Ma, J., Loke, H. K., Lingaraj, T., Wu, D., Hamman, K. B., Spelman, J. J., Cullis, C. A., Langston, S. P., Vyskocil, S., Sells, T. B., Mallender, W. D., Visiers, I., Li, P., Claiborne, C. F., Rolfe, M., Bolen, J. B., and Dick, L. R. (2010) Mol. Cell 37, 102-111). In the present study, substrate-assisted inhibition of human UAE (Ube1) by another adenosine sulfamate analogue, 5'-O-sulfamoyl-N(6)-[(1S)-2,3-dihydro-1H-inden-1-yl]-adenosine (Compound I), a nonselective E1 inhibitor, was characterized. Compound I inhibited UAE-dependent ATP-PP(i) exchange activity, caused loss of UAE thioester, and inhibited E1-E2 transthiolation in a dose-dependent manner. Mechanistic studies on Compound I and its purified ubiquitin adduct demonstrate that the proposed substrate-assisted inhibition via covalent adduct formation is entirely consistent with the three-step ubiquitin activation process and that the adduct is formed via nucleophilic attack of UAE thioester by the sulfamate group of Compound I after completion of step 2. Kinetic and affinity analysis of Compound I, MLN4924, and their purified ubiquitin adducts suggest that both the rate of adduct formation and the affinity between the adduct and E1 contribute to the overall potency. Because all E1s are thought to use a similar mechanism to activate their cognate ubiquitin-like proteins, the substrate-assisted inhibition by adenosine sulfamate analogues represents a promising strategy to develop potent and selective E1 inhibitors that can modulate diverse biological pathways." @default.
• W2160168027 created "2016-06-24" @default.
• W2160168027 creator A5009731683 @default.
• W2160168027 creator A5011506026 @default.
• W2160168027 creator A5016016965 @default.
• W2160168027 creator A5016504937 @default.
• W2160168027 creator A5020255092 @default.
• W2160168027 creator A5028939266 @default.
• W2160168027 creator A5031080907 @default.
• W2160168027 creator A5043732735 @default.
• W2160168027 creator A5045357859 @default.
• W2160168027 creator A5056722524 @default.
• W2160168027 creator A5057392250 @default.
• W2160168027 creator A5062887885 @default.
• W2160168027 creator A5071382485 @default.
• W2160168027 creator A5073070877 @default.
• W2160168027 creator A5076440243 @default.
• W2160168027 creator A5085586802 @default.
• W2160168027 date "2011-11-01" @default.
• W2160168027 modified "2023-10-16" @default.
• W2160168027 title "Mechanistic Studies of Substrate-assisted Inhibition of Ubiquitin-activating Enzyme by Adenosine Sulfamate Analogues" @default.
• W2160168027 cites W1539814399 @default.
• W2160168027 cites W1549578642 @default.
• W2160168027 cites W1553797204 @default.
• W2160168027 cites W1603251764 @default.
• W2160168027 cites W1968887194 @default.
• W2160168027 cites W1979250970 @default.
• W2160168027 cites W1987129537 @default.
• W2160168027 cites W1988820070 @default.
• W2160168027 cites W1991103963 @default.
• W2160168027 cites W1991841644 @default.
• W2160168027 cites W1994608712 @default.
• W2160168027 cites W1999353132 @default.
• W2160168027 cites W2004812160 @default.
• W2160168027 cites W2020031294 @default.
• W2160168027 cites W2022142478 @default.
• W2160168027 cites W2024249948 @default.
• W2160168027 cites W2067246673 @default.
• W2160168027 cites W2067271823 @default.
• W2160168027 cites W2076159058 @default.
• W2160168027 cites W2076194625 @default.
• W2160168027 cites W2080939719 @default.
• W2160168027 cites W2086851301 @default.
• W2160168027 cites W2092011356 @default.
• W2160168027 cites W2092265639 @default.
• W2160168027 cites W2095632153 @default.
• W2160168027 cites W2120380960 @default.
• W2160168027 cites W2122342459 @default.
• W2160168027 cites W2123077018 @default.
• W2160168027 cites W2132485651 @default.
• W2160168027 cites W2171186199 @default.
• W2160168027 cites W98415201 @default.
• W2160168027 doi "https://doi.org/10.1074/jbc.m111.279984" @default.
• W2160168027 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3220466" @default.
• W2160168027 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21969368" @default.
• W2160168027 hasPublicationYear "2011" @default.
• W2160168027 type Work @default.
• W2160168027 sameAs 2160168027 @default.
• W2160168027 citedByCount "79" @default.
• W2160168027 countsByYear W21601680272012 @default.
• W2160168027 countsByYear W21601680272013 @default.
• W2160168027 countsByYear W21601680272014 @default.
• W2160168027 countsByYear W21601680272015 @default.
• W2160168027 countsByYear W21601680272016 @default.
• W2160168027 countsByYear W21601680272017 @default.
• W2160168027 countsByYear W21601680272018 @default.
• W2160168027 countsByYear W21601680272019 @default.
• W2160168027 countsByYear W21601680272020 @default.
• W2160168027 countsByYear W21601680272021 @default.
• W2160168027 countsByYear W21601680272022 @default.
• W2160168027 countsByYear W21601680272023 @default.
• W2160168027 crossrefType "journal-article" @default.
• W2160168027 hasAuthorship W2160168027A5009731683 @default.
• W2160168027 hasAuthorship W2160168027A5011506026 @default.
• W2160168027 hasAuthorship W2160168027A5016016965 @default.
• W2160168027 hasAuthorship W2160168027A5016504937 @default.
• W2160168027 hasAuthorship W2160168027A5020255092 @default.
• W2160168027 hasAuthorship W2160168027A5028939266 @default.
• W2160168027 hasAuthorship W2160168027A5031080907 @default.
• W2160168027 hasAuthorship W2160168027A5043732735 @default.
• W2160168027 hasAuthorship W2160168027A5045357859 @default.
• W2160168027 hasAuthorship W2160168027A5056722524 @default.
• W2160168027 hasAuthorship W2160168027A5057392250 @default.
• W2160168027 hasAuthorship W2160168027A5062887885 @default.
• W2160168027 hasAuthorship W2160168027A5071382485 @default.
• W2160168027 hasAuthorship W2160168027A5073070877 @default.
• W2160168027 hasAuthorship W2160168027A5076440243 @default.
• W2160168027 hasAuthorship W2160168027A5085586802 @default.
• W2160168027 hasBestOaLocation W21601680271 @default.
• W2160168027 hasConcept C104317684 @default.
• W2160168027 hasConcept C108204754 @default.
• W2160168027 hasConcept C178790620 @default.
• W2160168027 hasConcept C180577832 @default.
• W2160168027 hasConcept C181199279 @default.
• W2160168027 hasConcept C185592680 @default.
• W2160168027 hasConcept C18903297 @default.
• W2160168027 hasConcept C25602115 @default.
• W2160168027 hasConcept C2776991684 @default.

• next