3UO9
Crystal Structure of Human GAC in Complex with Glutamate and BPTES
Summary for 3UO9
| Entry DOI | 10.2210/pdb3uo9/pdb |
| Related | 3UNW |
| Descriptor | Glutaminase kidney isoform, mitochondrial, GLYCEROL, N,N'-[sulfanediylbis(ethane-2,1-diyl-1,3,4-thiadiazole-5,2-diyl)]bis(2-phenylacetamide), ... (4 entities in total) |
| Functional Keywords | hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Isoform 1: Cytoplasm, cytosol. Isoform 3: Mitochondrion: O94925 |
| Total number of polymer chains | 4 |
| Total formula weight | 237169.71 |
| Authors | DeLaBarre, B.,Gross, S.,Cheng, F.,Gao, Y.,Jha, A.,Jiang, F.,Song, J.J.,Wei, W.,Hurov, J.B. (deposition date: 2011-11-16, release date: 2011-12-07, Last modification date: 2024-02-28) |
| Primary citation | DeLaBarre, B.,Gross, S.,Fang, C.,Gao, Y.,Jha, A.,Jiang, F.,Song J, J.,Wei, W.,Hurov, J.B. Full-length human glutaminase in complex with an allosteric inhibitor. Biochemistry, 50:10764-10770, 2011 Cited by PubMed 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. PubMed: 22049910DOI: 10.1021/bi201613d PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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