5w2j - Revision history

OCA at 14:13, 13 March 2024

OCA — Wed, 13 Mar 2024 14:13:30 GMT

←Older revision		Revision as of 14:13, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='5w2j' size='340' side='right'caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5w2j' size='340' side='right'caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5W2J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W2J FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.5Å</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=10090 LK3 transgenic mice])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5w2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2j OCA], [https://pdbe.org/5w2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w2j RCSB], [https://www.ebi.ac.uk/pdbsum/5w2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2j 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=5w2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2j OCA], [~~http~~://pdbe.org/5w2j PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5w2j RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5w2j PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2j ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GLSK_MOUSE GLSK_MOUSE]] 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.<ref>PMID:16641247</ref> <ref>PMID:22373647</ref> <ref>PMID:22228304</ref>	+	[https://www.uniprot.org/uniprot/GLSK_MOUSE GLSK_MOUSE] 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.<ref>PMID:16641247</ref> <ref>PMID:22373647</ref> <ref>PMID:22228304</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Glutamine-derived carbon becomes available for anabolic biosynthesis in cancer cells via the hydrolysis of glutamine to glutamate, as catalyzed by GAC, a splice variant of kidney-type glutaminase (GLS). Thus, there is significant interest in understanding the regulation of GAC activity, with the suggestion being that higher order oligomerization is required for its activation. We used x-ray crystallography, together with site-directed mutagenesis, to determine the minimal enzymatic unit capable of robust catalytic activity. Mutagenesis of the helical interface between the two pairs of dimers comprising a GAC tetramer yielded a non-active, GAC dimer whose x-ray structure displays a stationary loop ("activation loop") essential for coupling the binding of allosteric activators like inorganic phosphate to catalytic activity. Further mutagenesis that removed constraints on the activation loop yielded a constitutively active dimer, providing clues regarding how the activation loop communicates with the active site, as well as with a peptide segment that serves as a "lid" to close off the active site following substrate binding. Our studies show that the formation of large GAC oligomers is not a pre-requisite for full enzymatic activity. They also offer a mechanism by which the binding of activators like inorganic phosphate enables the activation loop to communicate with the active site to ensure maximal rates of catalysis, and promotes the opening of the lid to achieve optimal product release. Moreover, these findings provide new insights into how other regulatory events might induce GAC activation within cancer cells.	+
-		+
-	Mechanistic Basis of Glutaminase Activation: A KEY ENZYME THAT PROMOTES GLUTAMINE METABOLISM IN CANCER CELLS.,Li Y, Erickson JW, Stalnecker CA, Katt WP, Huang Q, Cerione RA, Ramachandran S J Biol Chem. 2016 Sep 30;291(40):20900-20910. doi: 10.1074/jbc.M116.720268. Epub , 2016 Aug 19. PMID:27542409<ref>PMID:27542409</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5w2j" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Glutaminase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Cerione~~, R A~~]]	+	[[Category: Cerione RA]]
-	[[Category: Li, Y]]	+	[[Category: Li Y]]
-	~~[[Category: Glutamine metabolism]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 09:10, 18 December 2019

OCA — Wed, 18 Dec 2019 09:10:24 GMT

←Older revision		Revision as of 09:10, 18 December 2019
Line 1:		Line 1:

	==Crystal structure of dimeric form of mouse Glutaminase C==		==Crystal structure of dimeric form of mouse Glutaminase C==
-	<StructureSection load='5w2j' size='340' side='right' caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5w2j' size='340' side='right'caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2J FirstGlance]. <br>		<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2J FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5w2j" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5w2j" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glutaminase 3D structures\|Glutaminase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Glutaminase]]		[[Category: Glutaminase]]
		+	[[Category: Large Structures]]
	[[Category: Lk3 transgenic mice]]		[[Category: Lk3 transgenic mice]]
	[[Category: Cerione, R A]]		[[Category: Cerione, R A]]

OCA at 15:51, 27 February 2019

OCA — Wed, 27 Feb 2019 15:51:23 GMT

←Older revision		Revision as of 15:51, 27 February 2019
Line 3:		Line 3:
	<StructureSection load='5w2j' size='340' side='right' caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5w2j' size='340' side='right' caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2J FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2J FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=10090 LK3 transgenic mice])</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=5w2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2j OCA], [http://pdbe.org/5w2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w2j RCSB], [http://www.ebi.ac.uk/pdbsum/5w2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2j 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=5w2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2j OCA], [http://pdbe.org/5w2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w2j RCSB], [http://www.ebi.ac.uk/pdbsum/5w2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2j ProSAT]</span></td></tr>
Line 24:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Glutaminase]]		[[Category: Glutaminase]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Cerione, R A]]		[[Category: Cerione, R A]]
	[[Category: Li, Y]]		[[Category: Li, Y]]
	[[Category: Glutamine metabolism]]		[[Category: Glutamine metabolism]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 07:49, 17 October 2018

OCA — Wed, 17 Oct 2018 07:49:55 GMT

←Older revision		Revision as of 07:49, 17 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5w2j is ~~ON HOLD~~	+	==Crystal structure of dimeric form of mouse Glutaminase C==
		+	<StructureSection load='5w2j' size='340' side='right' caption='[[5w2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5w2j]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W2J FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5w2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w2j OCA], [http://pdbe.org/5w2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w2j RCSB], [http://www.ebi.ac.uk/pdbsum/5w2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w2j ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GLSK_MOUSE GLSK_MOUSE]] 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.<ref>PMID:16641247</ref> <ref>PMID:22373647</ref> <ref>PMID:22228304</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Glutamine-derived carbon becomes available for anabolic biosynthesis in cancer cells via the hydrolysis of glutamine to glutamate, as catalyzed by GAC, a splice variant of kidney-type glutaminase (GLS). Thus, there is significant interest in understanding the regulation of GAC activity, with the suggestion being that higher order oligomerization is required for its activation. We used x-ray crystallography, together with site-directed mutagenesis, to determine the minimal enzymatic unit capable of robust catalytic activity. Mutagenesis of the helical interface between the two pairs of dimers comprising a GAC tetramer yielded a non-active, GAC dimer whose x-ray structure displays a stationary loop ("activation loop") essential for coupling the binding of allosteric activators like inorganic phosphate to catalytic activity. Further mutagenesis that removed constraints on the activation loop yielded a constitutively active dimer, providing clues regarding how the activation loop communicates with the active site, as well as with a peptide segment that serves as a "lid" to close off the active site following substrate binding. Our studies show that the formation of large GAC oligomers is not a pre-requisite for full enzymatic activity. They also offer a mechanism by which the binding of activators like inorganic phosphate enables the activation loop to communicate with the active site to ensure maximal rates of catalysis, and promotes the opening of the lid to achieve optimal product release. Moreover, these findings provide new insights into how other regulatory events might induce GAC activation within cancer cells.

-	~~Authors~~: ~~Cerione, R.~~A., Li, Y.	+	Mechanistic Basis of Glutaminase Activation: A KEY ENZYME THAT PROMOTES GLUTAMINE METABOLISM IN CANCER CELLS.,Li Y, Erickson JW, Stalnecker CA, Katt WP, Huang Q, Cerione RA, Ramachandran S J Biol Chem. 2016 Sep 30;291(40):20900-20910. doi: 10.1074/jbc.M116.720268. Epub , 2016 Aug 19. PMID:27542409<ref>PMID:27542409</ref>

-	~~Description: Crystal structure~~ of ~~dimeric form~~ of ~~mouse~~ Glutaminase C	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5w2j" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Glutaminase]]
		+	[[Category: Cerione, R A]]
	[[Category: Li, Y]]		[[Category: Li, Y]]
-	[[Category: ~~Cerione, R.A~~]]	+	[[Category: Glutamine metabolism]]
		+	[[Category: Hydrolase]]

OCA: Protected "5w2j" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:22:12 GMT

Protected "5w2j" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:22, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5w2j is ON HOLD Authors: Cerione, R.A., Li, Y. Description: Crystal structure of dimeric form of mouse Glutaminase C [[Category: Unreleased Structu...

OCA — Wed, 27 Sep 2017 14:22:10 GMT

New page: '''Unreleased structure''' The entry 5w2j is ON HOLD Authors: Cerione, R.A., Li, Y. Description: Crystal structure of dimeric form of mouse Glutaminase C [[Category: Unreleased Structu...

New page

'''Unreleased structure'''

The entry 5w2j is ON HOLD

Authors: Cerione, R.A., Li, Y.

Description: Crystal structure of dimeric form of mouse Glutaminase C
[[Category: Unreleased Structures]]
[[Category: Li, Y]]
[[Category: Cerione, R.A]]