3ss3 | pdb_00003ss3

Crystal structure of mouse Glutaminase C, ligand-free form

spinqualitylabelsall models 3ss3, resolution 2.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ss3 is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL Related: 3ss4, 3ss5 Gene: Gls, GLS1, mKIAA0838 (LK3 transgenic mice) Activity: Glutaminase, with EC number 3.5.1.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GLSK_MOUSE] Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Publication Abstract from PubMed Glutamine is an essential nutrient for cancer cell proliferation, especially in the context of citric acid cycle anaplerosis. In this manuscript we present results that collectively demonstrate that, of the three major mammalian glutaminases identified to date, the lesser studied splice variant of the gene gls, known as Glutaminase C (GAC), is important for tumor metabolism. We show that, although levels of both the kidney-type isoforms are elevated in tumor vs. normal tissues, GAC is distinctly mitochondrial. GAC is also most responsive to the activator inorganic phosphate, the content of which is supposedly higher in mitochondria subject to hypoxia. Analysis of X-ray crystal structures of GAC in different bound states suggests a mechanism that introduces the tetramerization-induced lifting of a "gating loop" as essential for the phosphate-dependent activation process. Surprisingly, phosphate binds inside the catalytic pocket rather than at the oligomerization interface. Phosphate also mediates substrate entry by competing with glutamate. A greater tendency to oligomerize differentiates GAC from its alternatively spliced isoform and the cycling of phosphate in and out of the active site distinguishes it from the liver-type isozyme, which is known to be less dependent on this ion. Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism.,Cassago A, Ferreira AP, Ferreira IM, Fornezari C, Gomes ER, Greene KS, Pereira HM, Garratt RC, Dias SM, Ambrosio AL Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1092-7. Epub 2012 Jan 6. PMID:22228304 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutaminase

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