5uqe - Revision history

OCA at 14:28, 6 March 2024

OCA — Wed, 06 Mar 2024 14:28:36 GMT

←Older revision		Revision as of 14:28, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5uqe' size='340' side='right'caption='[[5uqe]], [[Resolution\|resolution]] 3.60Å' scene=''>		<StructureSection load='5uqe' size='340' side='right'caption='[[5uqe]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uqe]] is a 5 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=5UQE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5UQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uqe]] is a 5 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=5UQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UQE FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=04A:N~~,N-[~~SULFANEDIYLBIS(ETHANE-2,1-DIYL-1,~~3~~,4-THIADIAZOLE-5,2-DIYL)]BIS(2-PHENYLACETAMIDE)'>04A</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]] 3.6Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=04A:N,N-[SULFANEDIYLBIS(ETHANE-2,1-DIYL-1,3,4-THIADIAZOLE-5,2-DIYL)]BIS(2-PHENYLACETAMIDE)'>04A</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5uqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqe OCA], [https://pdbe.org/5uqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uqe RCSB], [https://www.ebi.ac.uk/pdbsum/5uqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqe ProSAT]</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=5uqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqe OCA], [~~http~~://pdbe.org/5uqe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5uqe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5uqe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqe 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;">~~	+
-	~~== 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<ref>PMID:28526749</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5uqe" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Glutaminase 3D structures\|Glutaminase 3D structures]]		*[[Glutaminase 3D structures\|Glutaminase 3D structures]]
-	== References ==
-	<references/>
	__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: Pasquali~~, C C]]~~	+	[[Category: Pasquali CC]]
-	~~[[Category: Gl]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Kga]]~~	+
-	~~[[Category: Kidney-type~~]]	+

OCA at 09:21, 1 January 2020

OCA — Wed, 01 Jan 2020 09:21:11 GMT

←Older revision		Revision as of 09:21, 1 January 2020
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Glutaminase\|Glutaminase]]	+	*[[Glutaminase 3D structures\|Glutaminase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:28, 17 April 2019

OCA — Wed, 17 Apr 2019 06:28:26 GMT

←Older revision		Revision as of 06:28, 17 April 2019
Line 1:		Line 1:

	==Multidomain structure of human kidney-type glutaminase(KGA/GLS)==		==Multidomain structure of human kidney-type glutaminase(KGA/GLS)==
-	<StructureSection load='5uqe' size='340' side='right' caption='[[5uqe]], [[Resolution\|resolution]] 3.60Å' scene=''>	+	<StructureSection load='5uqe' size='340' side='right'caption='[[5uqe]], [[Resolution\|resolution]] 3.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5uqe]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5uqe]] is a 5 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=5UQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UQE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=04A:N,N-[SULFANEDIYLBIS(ETHANE-2,1-DIYL-1,3,4-THIADIAZOLE-5,2-DIYL)]BIS(2-PHENYLACETAMIDE)'>04A</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=04A:N,N-[SULFANEDIYLBIS(ETHANE-2,1-DIYL-1,3,4-THIADIAZOLE-5,2-DIYL)]BIS(2-PHENYLACETAMIDE)'>04A</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='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='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=5uqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqe OCA], [http://pdbe.org/5uqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uqe RCSB], [http://www.ebi.ac.uk/pdbsum/5uqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqe ProSAT]</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=5uqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqe OCA], [http://pdbe.org/5uqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uqe RCSB], [http://www.ebi.ac.uk/pdbsum/5uqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqe ProSAT]</span></td></tr>
Line 10:		Line 11:
	== 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.		[[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.
		+	<div style="background-color:#fffaf0;">
		+	== 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<ref>PMID:28526749</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5uqe" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glutaminase\|Glutaminase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Glutaminase]]		[[Category: Glutaminase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Ambrosio, A L.B]]		[[Category: Ambrosio, A L.B]]
	[[Category: Dias, S M.G]]		[[Category: Dias, S M.G]]
	[[Category: Pasquali, C C]]		[[Category: Pasquali, C C]]
	[[Category: Gl]]		[[Category: Gl]]
-	[[Category: Human]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Kga]]		[[Category: Kga]]
	[[Category: Kidney-type]]		[[Category: Kidney-type]]

OCA at 11:15, 3 August 2017

OCA — Thu, 03 Aug 2017 11:15:22 GMT

←Older revision		Revision as of 11:15, 3 August 2017
Line 15:		Line 15:
	[[Category: Ambrosio, A L.B]]		[[Category: Ambrosio, A L.B]]
	[[Category: Dias, S M.G]]		[[Category: Dias, S M.G]]
-	[[Category: ~~Pascoal~~, C C]]	+	[[Category: Pasquali, C C]]
	[[Category: Gl]]		[[Category: Gl]]
	[[Category: Human]]		[[Category: Human]]

OCA at 13:50, 24 May 2017

OCA — Wed, 24 May 2017 13:50:09 GMT

←Older revision		Revision as of 13:50, 24 May 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5uqe is ~~ON HOLD~~	+	==Multidomain structure of human kidney-type glutaminase(KGA/GLS)==
-		+	<StructureSection load='5uqe' size='340' side='right' caption='[[5uqe]], [[Resolution\|resolution]] 3.60Å' scene=''>
-	~~Authors~~: ~~Pascoal~~, C.C., ~~Dias, S~~.M.G., ~~Ambrosio~~, A.L.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5uqe]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UQE FirstGlance]. <br>
-	~~Description~~: ~~Multidomain structure~~ of ~~human kidney~~-~~type glutaminase(KGA~~/~~GLS)~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=04A:N,N-[SULFANEDIYLBIS(ETHANE-2,1-DIYL-1,3,4-THIADIAZOLE-5,2-DIYL)]BIS(2-PHENYLACETAMIDE)'>04A</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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>
-	[[Category: ~~Pascoal~~, C.C]]	+	<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=5uqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uqe OCA], [http://pdbe.org/5uqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uqe RCSB], [http://www.ebi.ac.uk/pdbsum/5uqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uqe ProSAT]</span></td></tr>
-	[[Category: Dias, S.M.G]]	+	</table>
-	[[Category: ~~Ambrosio~~, ~~A.L.B~~]]	+	== 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.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Glutaminase]]
		+	[[Category: Ambrosio, A L.B]]
		+	[[Category: Dias, S M.G]]
		+	[[Category: Pascoal, C C]]
		+	[[Category: Gl]]
		+	[[Category: Human]]
		+	[[Category: Hydrolase]]
		+	[[Category: Kga]]
		+	[[Category: Kidney-type]]

OCA at 19:17, 15 March 2017

OCA — Wed, 15 Mar 2017 19:17:36 GMT

←Older revision		Revision as of 19:17, 15 March 2017
Line 7:		Line 7:
	Description: Multidomain structure of human kidney-type glutaminase(KGA/GLS)		Description: Multidomain structure of human kidney-type glutaminase(KGA/GLS)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Ambrosio, A.L.B]]
	[[Category: Pascoal, C.C]]		[[Category: Pascoal, C.C]]
	[[Category: Dias, S.M.G]]		[[Category: Dias, S.M.G]]
		+	[[Category: Ambrosio, A.L.B]]

OCA: Protected "5uqe" [edit=sysop:move=sysop]

OCA — Thu, 09 Mar 2017 14:47:34 GMT

Protected "5uqe" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:47, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5uqe is ON HOLD Authors: Pascoal, C.C., Dias, S.M.G., Ambrosio, A.L.B. Description: Multidomain structure of human kidney-type glutaminase(KGA/GLS)...

OCA — Thu, 09 Mar 2017 14:47:32 GMT

New page: '''Unreleased structure''' The entry 5uqe is ON HOLD Authors: Pascoal, C.C., Dias, S.M.G., Ambrosio, A.L.B. Description: Multidomain structure of human kidney-type glutaminase(KGA/GLS)...

New page

'''Unreleased structure'''

The entry 5uqe is ON HOLD

Authors: Pascoal, C.C., Dias, S.M.G., Ambrosio, A.L.B.

Description: Multidomain structure of human kidney-type glutaminase(KGA/GLS)
[[Category: Unreleased Structures]]
[[Category: Ambrosio, A.L.B]]
[[Category: Pascoal, C.C]]
[[Category: Dias, S.M.G]]