Literature summary for 3.5.1.2 extracted from

Cassago, A.; Ferreira, A.P.; Ferreira, I.M.; Fornezari, C.; Gomes, E.R.; Greene, K.S.; Pereira, H.M.; Garratt, R.C.; Dias, S.M.; Ambrosio, A.L.
Mitochondrial localization and structure-based phosphate activation mechanism of glutaminase C with implications for cancer metabolism (2012), Proc. Natl. Acad. Sci. USA, 109, 1092-1097.

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Activating Compound

Activating Compound	Comment	Organism	Structure
phosphate	structure-based phosphate activation mechanism of GAC and GLS1/KGA, introducing the tetramerization-induced lifting of a gating loop essential for the phosphate-dependent activation process, overview. Phosphate binds inside the catalytic pocket rather than at the oligomerization interface. Phosphate also mediates substrate entry by competing with glutamate. GLS1/KGA is as effective as GLS2/LGA, but presents an eightfold gain in efficiency at 50 mM phosphate, with kcat-app/Km-app of 0.4 mM/s and 17.6 mM/s, respectively. One ion bound per monomer, buried inside the highly positive active site where it makes polar contacts with Ser291, Asn340 and Tyr471, and two water molecules	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
phosphate- and L-glutamate-bound GAC, X-ray diffraction structure determination and analysis at 2.85 A and 2.80 A resolution, respectively	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
F327S	the gain-of-function GAC mutant shows a Km as low as 8.2 mM, even in the absence of phosphate and at only 5 nM protein concentration	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	kinetics, overview	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytoplasm	KGA	Homo sapiens	5737	-
mitochondrion	GAC is mitochondrial, distinctly localized from kidney-type GLS isozymes	Homo sapiens	5739	-
additional information	KGA and GAC are enhanced in cancer, but only GAC is found in mitochondria	Homo sapiens	-	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
chloride	competes with phosphate for binding to the catalytic Ser291, at high concentration (500 mM NaCl) it can dislodge phosphate from its site and shift the protein equilibrium to lower-order oligomers	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	kidney-type glutaminase, KGA or GLS1, glutaminase C, GAC, a splice variant of the gene gls encoding GLS1, and liver-type glutaminase GLS2	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
A-549 cell	kidney-type glutaminase GLS1	Homo sapiens	-
DU-145 cell	kidney-type glutaminase GLS1	Homo sapiens	-
kidney	kidney-type glutaminase GLS1 and glutaminase C	Homo sapiens	-
liver	liver-type glutaminase GLS2	Homo sapiens	-
MDA-MB-231 cell	kidney-type glutaminase GLS1	Homo sapiens	-
additional information	KGA and GAC are enhanced in cancer, but only GAC is found in mitochondria	Homo sapiens	-
PC-3 cell	kidney-type glutaminase GLS1	Homo sapiens	-
SK-BR-3 cell	kidney-type glutaminase GLS1	Homo sapiens	-

Subunits

Subunits	Comment	Organism
More	structure of ligand-free GAC, molecular replacement, overview. Accompanying tetramer assembly, conformational changes involving Phe327 are triggered, lifting the gating loop and exposing the active site	Homo sapiens
tetramer	the side chain of Phe327, which in all monomers, is part of a hydrophobic cluster located at the tetramer interface, formed by the complementary stacking of Phe327 itself, Ala395, Ile396, Tyr399, in chain A, with its equivalent residues in chain D	Homo sapiens

Synonyms

Synonyms	Comment	Organism
GAC	-	Homo sapiens
GLS1	-	Homo sapiens
GLS2	-	Homo sapiens
glutaminase C	-	Homo sapiens
KGA	-	Homo sapiens
kidney-type glutaminase	-	Homo sapiens
LGA	-	Homo sapiens
liver-type glitaminase	-	Homo sapiens

General Information

General Information	Comment	Organism
metabolism	glutaminase C is the first enzyme in glutaminolysis	Homo sapiens
physiological function	glutaminase C is important for tumor metabolism. Glutamate production by mitochondrial glutaminase C, the first enzyme in glutaminolysis, is a key process for body homeostasis, and a crucial carbon donor for amino acid and lipid synthesis in tumor cells	Homo sapiens

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Release 2023.1 (January 2023)