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| | <StructureSection load='5u0j' size='340' side='right'caption='[[5u0j]], [[Resolution|resolution]] 1.72Å' scene=''> | | <StructureSection load='5u0j' size='340' side='right'caption='[[5u0j]], [[Resolution|resolution]] 1.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u0j]] is a 4 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=5U0J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U0J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u0j]] is a 4 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=5U0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U0J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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]] 1.72Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u0i|5u0i]], [[5u0k|5u0k]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLS, GLS1, KIAA0838 ([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=5u0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u0j OCA], [https://pdbe.org/5u0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u0j RCSB], [https://www.ebi.ac.uk/pdbsum/5u0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u0j 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=5u0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u0j OCA], [http://pdbe.org/5u0j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u0j RCSB], [http://www.ebi.ac.uk/pdbsum/5u0j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u0j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLSK_HUMAN GLSK_HUMAN]] 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. Isoform 2 lacks catalytic activity. | + | [https://www.uniprot.org/uniprot/GLSK_HUMAN GLSK_HUMAN] 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. Isoform 2 lacks catalytic activity. |
| | <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: Gonzalez, A]] | + | [[Category: Gonzalez A]] |
| - | [[Category: Pasquali, C C]] | + | [[Category: Pasquali CC]] |
| - | [[Category: Ankyrin]]
| + | |
| - | [[Category: Gls1]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
GLSK_HUMAN 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. Isoform 2 lacks catalytic activity.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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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