Artikel ; Online: Full-length human glutaminase in complex with an allosteric inhibitor.
2011 Band 50, Heft 50, Seite(n) 10764–10770
Abstract: Glutaminase (GLS1/2) catalyzes the conversion of L-glutamine to L-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido-1,2,4,thiadiazol-2-yl)ethyl ...
Abstract | Glutaminase (GLS1/2) catalyzes the conversion of L-glutamine to L-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido-1,2,4,thiadiazol-2-yl)ethyl sulfide (BPTES). We report here the first full-length crystal structure of GAC in the presence and absence of BPTES molecules. Two BPTES molecules bind at an interface region of the GAC tetramer in a manner that appears to lock the GAC tetramer into a nonproductive conformation. The importance of these loops with regard to overall enzymatic activity of the tetramer was revealed by a series of GAC point mutants designed to create a BPTES resistant GAC. |
|||||
---|---|---|---|---|---|---|
Mesh-Begriff(e) | Allosteric Site ; Amino Acid Sequence ; Amino Acid Substitution ; Biocatalysis ; Databases, Protein ; Dimerization ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/metabolism ; Glutaminase/antagonists & inhibitors ; Glutaminase/chemistry ; Glutaminase/genetics ; Glutaminase/metabolism ; Humans ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/chemistry ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutant Proteins/antagonists & inhibitors ; Mutant Proteins/chemistry ; Mutant Proteins/metabolism ; Point Mutation ; Protein Conformation ; Recombinant Proteins/antagonists & inhibitors ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Sequence Alignment ; Sulfides/chemistry ; Sulfides/metabolism ; Thiadiazoles/chemistry ; Thiadiazoles/metabolism | |||||
Chemische Substanzen | Enzyme Inhibitors ; Isoenzymes ; Mutant Proteins ; Recombinant Proteins ; Sulfides ; Thiadiazoles ; bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide ; Glutaminase (EC 3.5.1.2) | |||||
Sprache | Englisch | |||||
Erscheinungsdatum | 2011-12-20 | |||||
Erscheinungsland | United States | |||||
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't | |||||
ZDB-ID | 1108-3 | |||||
ISSN | 1520-4995 ; 0006-2960 | |||||
ISSN (online) | 1520-4995 | |||||
ISSN | 0006-2960 | |||||
DOI | 10.1021/bi201613d | |||||
Signatur |
|
|||||
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
Zs.A 217: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.