Matches in SemOpenAlex for { <https://semopenalex.org/work/W2032035823> ?p ?o ?g. }
- W2032035823 endingPage "5161" @default.
- W2032035823 startingPage "5155" @default.
- W2032035823 abstract "Diphtheria toxin (DT) has been studied as a model for understanding active-site structure and function in the ADP-ribosyltransferases. Earlier evidence suggested that histidine-21 of DT is important for the ADP-ribosylation of eukaryotic elongation factor 2 (EF-2). We have generated substitutions of this residue by cassette mutagenesis of a synthetic gene encoding the catalytic A fragment (DTA) of DT, and have characterized purified mutant forms of this domain. Changing histidine-21 to alanine, aspartic acid, leucine, glutamine, or arginine diminished ADP-ribosylation activity by 70-fold or greater. In contrast, asparagine proved to be a functionally conservative substitution, which reduced ADP-ribosylation activity by < 3-fold. The asparagine mutant was approximately 50-fold-attenuated in NAD glycohydrolase activity, however. Dissociation constants (Kd) for NAD binding, determined by quenching of the intrinsic protein fluorescence, were 15 microM for wild-type DTA, 160 microM for the asparagine mutant, and greater than 500 microM NAD for the alanine, leucine, glutamine, and arginine mutants. These and previous results support a model of the ADP-ribosylation of EF-2 in which histidine-21 serves primarily a hydrogen-bonding function. We propose that the pi-imidazole nitrogen of His-21 hydrogen-bonds to the nicotinamide carboxamide, orienting the N-glycosidic bond of NAD for attack by the incoming nucleophile in a direct displacement mechanism, and then stabilizing the transition-state intermediate of this reaction." @default.
- W2032035823 created "2016-06-24" @default.
- W2032035823 creator A5005685657 @default.
- W2032035823 creator A5016273790 @default.
- W2032035823 creator A5016429805 @default.
- W2032035823 creator A5030582764 @default.
- W2032035823 creator A5031050782 @default.
- W2032035823 creator A5081998850 @default.
- W2032035823 date "1994-05-01" @default.
- W2032035823 modified "2023-09-26" @default.
- W2032035823 title "Active-Site Mutations of the Diphtheria Toxin Catalytic Domain: Role of Histidine-21 in Nicotinamide Adenine Dinucleotide Binding and ADP-Ribosylation of Elongation Factor 2" @default.
- W2032035823 cites W1495405792 @default.
- W2032035823 cites W1500549143 @default.
- W2032035823 cites W1510351771 @default.
- W2032035823 cites W1523445848 @default.
- W2032035823 cites W1528142343 @default.
- W2032035823 cites W1531686808 @default.
- W2032035823 cites W1545162664 @default.
- W2032035823 cites W1565594466 @default.
- W2032035823 cites W1567594253 @default.
- W2032035823 cites W1568523124 @default.
- W2032035823 cites W1590641803 @default.
- W2032035823 cites W1596298885 @default.
- W2032035823 cites W1608918896 @default.
- W2032035823 cites W1842213437 @default.
- W2032035823 cites W1965992951 @default.
- W2032035823 cites W1974988689 @default.
- W2032035823 cites W1975804033 @default.
- W2032035823 cites W1977993125 @default.
- W2032035823 cites W1982231816 @default.
- W2032035823 cites W1991958052 @default.
- W2032035823 cites W1993285746 @default.
- W2032035823 cites W1998431483 @default.
- W2032035823 cites W2000857527 @default.
- W2032035823 cites W2019218430 @default.
- W2032035823 cites W2023148539 @default.
- W2032035823 cites W2027339215 @default.
- W2032035823 cites W2030482992 @default.
- W2032035823 cites W2034637992 @default.
- W2032035823 cites W2054507895 @default.
- W2032035823 cites W2056121463 @default.
- W2032035823 cites W2072767834 @default.
- W2032035823 cites W2075485926 @default.
- W2032035823 cites W2090561081 @default.
- W2032035823 cites W2092002806 @default.
- W2032035823 cites W2092494663 @default.
- W2032035823 cites W2143567517 @default.
- W2032035823 cites W2319566190 @default.
- W2032035823 doi "https://doi.org/10.1021/bi00183a019" @default.
- W2032035823 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8172890" @default.
- W2032035823 hasPublicationYear "1994" @default.
- W2032035823 type Work @default.
- W2032035823 sameAs 2032035823 @default.
- W2032035823 citedByCount "53" @default.
- W2032035823 countsByYear W20320358232012 @default.
- W2032035823 countsByYear W20320358232013 @default.
- W2032035823 countsByYear W20320358232014 @default.
- W2032035823 countsByYear W20320358232015 @default.
- W2032035823 countsByYear W20320358232017 @default.
- W2032035823 countsByYear W20320358232019 @default.
- W2032035823 countsByYear W20320358232020 @default.
- W2032035823 countsByYear W20320358232021 @default.
- W2032035823 countsByYear W20320358232022 @default.
- W2032035823 crossrefType "journal-article" @default.
- W2032035823 hasAuthorship W2032035823A5005685657 @default.
- W2032035823 hasAuthorship W2032035823A5016273790 @default.
- W2032035823 hasAuthorship W2032035823A5016429805 @default.
- W2032035823 hasAuthorship W2032035823A5030582764 @default.
- W2032035823 hasAuthorship W2032035823A5031050782 @default.
- W2032035823 hasAuthorship W2032035823A5081998850 @default.
- W2032035823 hasConcept C181199279 @default.
- W2032035823 hasConcept C185592680 @default.
- W2032035823 hasConcept C2775895851 @default.
- W2032035823 hasConcept C2776901170 @default.
- W2032035823 hasConcept C2777367657 @default.
- W2032035823 hasConcept C2778460671 @default.
- W2032035823 hasConcept C2779728014 @default.
- W2032035823 hasConcept C2779856020 @default.
- W2032035823 hasConcept C33057221 @default.
- W2032035823 hasConcept C41183919 @default.
- W2032035823 hasConcept C45510557 @default.
- W2032035823 hasConcept C515207424 @default.
- W2032035823 hasConcept C55493867 @default.
- W2032035823 hasConcept C71240020 @default.
- W2032035823 hasConcept C75520062 @default.
- W2032035823 hasConceptScore W2032035823C181199279 @default.
- W2032035823 hasConceptScore W2032035823C185592680 @default.
- W2032035823 hasConceptScore W2032035823C2775895851 @default.
- W2032035823 hasConceptScore W2032035823C2776901170 @default.
- W2032035823 hasConceptScore W2032035823C2777367657 @default.
- W2032035823 hasConceptScore W2032035823C2778460671 @default.
- W2032035823 hasConceptScore W2032035823C2779728014 @default.
- W2032035823 hasConceptScore W2032035823C2779856020 @default.
- W2032035823 hasConceptScore W2032035823C33057221 @default.
- W2032035823 hasConceptScore W2032035823C41183919 @default.
- W2032035823 hasConceptScore W2032035823C45510557 @default.
- W2032035823 hasConceptScore W2032035823C515207424 @default.
- W2032035823 hasConceptScore W2032035823C55493867 @default.