Literature summary for 3.5.1.2 extracted from

Thangavelu, K.; Pan, C.Q.; Karlberg, T.; Balaji, G.; Uttamchandani, M.; Suresh, V.; Schueler, H.; Low, B.C.; Sivaraman, J.
Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism (2012), Proc. Natl. Acad. Sci. USA, 109, 7705-7710.

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Activating Compound

Activating Compound	Comment	Organism	Structure
Epidermal growth factor	kidney-type glutaminase activity in cells is stimulated by EGF	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
expression of HA-tagged or FLAG-tagged wild-type and mutant kidney-type glutaminase in 293T cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
L321A/F322A/L323	site-directed mutagenesis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide	i.e. BPTES, binds to an allosteric pocket at the dimer interface of kidney-type glutaminase, triggering a dramatic conformational change of the key loop (Glu312-Pro329) near the catalytic site and rendering it inactive, allosteric inhibition. Binding of BPTES stabilizes the inactive tetramers of the catalytic domain of kidney-type glutaminase. The binding mode of BPTES on the hydrophobic pocket determines its specificity to the kidney-type glutaminase isoform KGA	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-glutamine + H2O	Homo sapiens	-	L-glutamate + NH3	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	kidney-type glutaminase isoform KGA	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	phosphorylation-dependent regulation of kidney-type glutaminase	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
kidney	kidney-type glutaminase isoform KGA	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-glutamine + H2O	-	Homo sapiens	L-glutamate + NH3	-	?

Subunits

Subunits	Comment	Organism
dimer	active kidney-type glutaminase	Homo sapiens
tetramer	inactive kidney-type glutaminase	Homo sapiens

Synonyms

Synonyms	Comment	Organism
KGA	-	Homo sapiens
kidney-type glutaminase	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	treating cells that coexpressed Mek2-K101A and kidney-type glutaminase with suboptimal level of BPTES leads to synergistic inhibition on cell proliferation	Homo sapiens
additional information	Ile221-Leu533 is the catalytic domain of kidney-type glutaminase	Homo sapiens
physiological function	kidney-type glutaminase activity in cells is stimulated by EGF, and kidney-type glutaminase associates with all three kinase components of the Raf-1/Mek2/Erk signaling module, interaction mode, the bound ligand makes several hydrogen-bonding contacts to Gln285, Ser286, Asn335, Glu381, Asn388, Tyr414, Tyr466, and Val484, overview. The kidney-type glutaminase active and inhibitory sites show a dynamic nature, cross-talk and regulation of kidney-type glutaminase activities by EGF-mediated Raf-Mek-Erk signaling. The enhanced activity is abrogated by kinase-dead, dominant negative mutants of Raf-1 (Raf-1-K375M) andMek2 (Mek2-K101A), protein phosphatase PP2A, and Mek-inhibitor U0126, indicative of phosphorylation-dependent regulation. kidney-type glutaminase can interact equally well with the wild-type or mutant forms of Raf-1 and Mek2. The activity of kidney-type glutaminase is directly regulated by Raf-Mek-Erk downstream of EGF receptor	Homo sapiens

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Release 2023.1 (January 2023)