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| | <StructureSection load='5u0k' size='340' side='right'caption='[[5u0k]], [[Resolution|resolution]] 2.55Å' scene=''> | | <StructureSection load='5u0k' size='340' side='right'caption='[[5u0k]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u0k]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U0K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u0k]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U0K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U0K FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u0i|5u0i]], [[5u0j|5u0j]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.548Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLS2, GA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u0k OCA], [https://pdbe.org/5u0k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u0k RCSB], [https://www.ebi.ac.uk/pdbsum/5u0k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u0k ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutaminase Glutaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.2 3.5.1.2] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u0k OCA], [http://pdbe.org/5u0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u0k RCSB], [http://www.ebi.ac.uk/pdbsum/5u0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u0k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLSL_HUMAN GLSL_HUMAN]] Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.<ref>PMID:20378837</ref> | + | [https://www.uniprot.org/uniprot/GLSL_HUMAN GLSL_HUMAN] Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.<ref>PMID:20378837</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutaminase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ambrosio, A L.B]] | + | [[Category: Ambrosio ALB]] |
| - | [[Category: Dias, S M.G]] | + | [[Category: Dias SMG]] |
| - | [[Category: Ferreira, I M]] | + | [[Category: Ferreira IM]] |
| - | [[Category: Gonzalez, A]] | + | [[Category: Gonzalez A]] |
| - | [[Category: Pasquali, C C]] | + | [[Category: Pasquali CC]] |
| - | [[Category: Ankyrin]]
| + | |
| - | [[Category: Gls2]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
GLSL_HUMAN Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.[1]
Publication Abstract from PubMed
On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. However, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform, glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. To obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC. Collectively, these results provide information about glutaminases that may aid in the design of isoform-specific glutaminase inhibitors.
The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats.,Pasquali CC, Islam Z, Adamoski D, Ferreira IM, Righeto RD, Bettini J, Portugal RV, Yue WW, Gonzalez A, Dias SMG, Ambrosio ALB J Biol Chem. 2017 Jul 7;292(27):11572-11585. doi: 10.1074/jbc.M117.787291. Epub, 2017 May 19. PMID:28526749[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7455-60. doi:, 10.1073/pnas.1001006107. Epub 2010 Apr 8. PMID:20378837 doi:10.1073/pnas.1001006107
- ↑ Pasquali CC, Islam Z, Adamoski D, Ferreira IM, Righeto RD, Bettini J, Portugal RV, Yue WW, Gonzalez A, Dias SMG, Ambrosio ALB. The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats. J Biol Chem. 2017 Jul 7;292(27):11572-11585. doi: 10.1074/jbc.M117.787291. Epub, 2017 May 19. PMID:28526749 doi:http://dx.doi.org/10.1074/jbc.M117.787291
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