Full-length human glutaminase in complex with an allosteric inhibitor
Biochemistry, 2011•ACS Publications
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 …
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 …
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.
ACS Publications