5j5t - Revision history

OCA at 06:54, 3 April 2024

OCA — Wed, 03 Apr 2024 06:54:22 GMT

←Older revision		Revision as of 06:54, 3 April 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/M4K3_HUMAN M4K3_HUMAN] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.<ref>PMID:9275185</ref>		[https://www.uniprot.org/uniprot/M4K3_HUMAN M4K3_HUMAN] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.<ref>PMID:9275185</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Germinal-center kinase-like kinase (GLK, Map4k3), a GCK-I family kinase, plays multiple roles in regulating apoptosis, amino acid sensing, and immune signaling. We describe here the crystal structure of an activation loop mutant of GLK kinase domain bound to an inhibitor. The structure reveals a weakly associated, activation-loop swapped dimer with more than 20 amino acids of ordered density at the carboxy-terminus. This C-terminal PEST region binds intermolecularly to the hydrophobic groove of the N-terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an "active" kinase, including the salt bridge between the C-helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P-loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.
-
-	Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension.,Marcotte D, Rushe M, M Arduini R, Lukacs C, Atkins K, Sun X, Little K, Cullivan M, Paramasivam M, Patterson TA, Hesson T, D McKee T, May-Dracka TL, Xin Z, Bertolotti-Ciarlet A, Bhisetti GR, Lyssikatos JP, Silvian LF Protein Sci. 2016 Oct 11. doi: 10.1002/pro.3062. PMID:27727493<ref>PMID:27727493</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5j5t" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:49, 6 September 2023

OCA — Wed, 06 Sep 2023 10:49:49 GMT

←Older revision		Revision as of 10:49, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='5j5t' size='340' side='right'caption='[[5j5t]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='5j5t' size='340' side='right'caption='[[5j5t]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j5t]] is a 1 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=5J5T OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5J5T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j5t]] is a 1 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=5J5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J5T FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=6G2:5~~-[~~2-(PIPERIDIN-4-YL)-1,3-THIAZOL-5-YL~~]~~-3-[(PYRIDIN-4-YL)METHOXY~~]~~PYRIDIN-~~2~~-AMINE'>6G2</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]] 2.85Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~TPO~~:~~PHOSPHOTHREONINE'>TPO</scene></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6G2:5-[2-(PIPERIDIN-4-YL)-1,3-THIAZOL-5-YL]-3-[(PYRIDIN-4-YL)METHOXY]PYRIDIN-2-AMINE'>6G2</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>~~[~~[Gene\|Gene:]]</b></td><td class="sblockDat">MAP4K3~~, ~~RAB8IPL1 ([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=5j5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5t OCA], [https://pdbe.org/5j5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j5t RCSB], [https://www.ebi.ac.uk/pdbsum/5j5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5t 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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </~~span~~></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5j5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5t OCA], [~~http~~://pdbe.org/5j5t PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5j5t RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5j5t PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5t ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/M4K3_HUMAN M4K3_HUMAN]] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.<ref>PMID:9275185</ref>	+	[https://www.uniprot.org/uniprot/M4K3_HUMAN M4K3_HUMAN] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.<ref>PMID:9275185</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Marcotte D]]
-	[[Category: Marcotte, D]]	+	[[Category: Silvian LF]]
-	[[Category: Silvian~~, L F]]~~	+
-	~~[[Category: Protein kinsae]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:30, 10 June 2020

OCA — Wed, 10 Jun 2020 07:30:50 GMT

←Older revision		Revision as of 07:30, 10 June 2020
Line 1:		Line 1:

	==GLK co-crystal structure with aminopyrrolopyrimidine inhibitor==		==GLK co-crystal structure with aminopyrrolopyrimidine inhibitor==
-	<StructureSection load='5j5t' size='340' side='right' caption='[[5j5t]], [[Resolution\|resolution]] 2.85Å' scene=''>	+	<StructureSection load='5j5t' size='340' side='right'caption='[[5j5t]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5j5t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5T OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5J5T FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5j5t]] is a 1 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=5J5T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J5T FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6G2:5-[2-(PIPERIDIN-4-YL)-1,3-THIAZOL-5-YL]-3-[(PYRIDIN-4-YL)METHOXY]PYRIDIN-2-AMINE'>6G2</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6G2:5-[2-(PIPERIDIN-4-YL)-1,3-THIAZOL-5-YL]-3-[(PYRIDIN-4-YL)METHOXY]PYRIDIN-2-AMINE'>6G2</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP4K3, RAB8IPL1 ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5j5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5t OCA], [http://pdbe.org/5j5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5t RCSB], [http://www.ebi.ac.uk/pdbsum/5j5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5t ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5j5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5t OCA], [http://pdbe.org/5j5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5t RCSB], [http://www.ebi.ac.uk/pdbsum/5j5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5t ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Marcotte, D]]		[[Category: Marcotte, D]]

OCA at 18:33, 26 October 2016

OCA — Wed, 26 Oct 2016 18:33:12 GMT

←Older revision		Revision as of 18:33, 26 October 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5j5t is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==GLK co-crystal structure with aminopyrrolopyrimidine inhibitor==
		+	<StructureSection load='5j5t' size='340' side='right' caption='[[5j5t]], [[Resolution\|resolution]] 2.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5j5t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5J5T FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6G2:5-[2-(PIPERIDIN-4-YL)-1,3-THIAZOL-5-YL]-3-[(PYRIDIN-4-YL)METHOXY]PYRIDIN-2-AMINE'>6G2</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5j5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5t OCA], [http://pdbe.org/5j5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j5t RCSB], [http://www.ebi.ac.uk/pdbsum/5j5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5t ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M4K3_HUMAN M4K3_HUMAN]] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.<ref>PMID:9275185</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Germinal-center kinase-like kinase (GLK, Map4k3), a GCK-I family kinase, plays multiple roles in regulating apoptosis, amino acid sensing, and immune signaling. We describe here the crystal structure of an activation loop mutant of GLK kinase domain bound to an inhibitor. The structure reveals a weakly associated, activation-loop swapped dimer with more than 20 amino acids of ordered density at the carboxy-terminus. This C-terminal PEST region binds intermolecularly to the hydrophobic groove of the N-terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an "active" kinase, including the salt bridge between the C-helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P-loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.

-	~~Authors~~:	+	Germinal-center kinase-like kinase co-crystal structure reveals a swapped activation loop and C-terminal extension.,Marcotte D, Rushe M, M Arduini R, Lukacs C, Atkins K, Sun X, Little K, Cullivan M, Paramasivam M, Patterson TA, Hesson T, D McKee T, May-Dracka TL, Xin Z, Bertolotti-Ciarlet A, Bhisetti GR, Lyssikatos JP, Silvian LF Protein Sci. 2016 Oct 11. doi: 10.1002/pro.3062. PMID:27727493<ref>PMID:27727493</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5j5t" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Marcotte, D]]
		+	[[Category: Silvian, L F]]
		+	[[Category: Protein kinsae]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 15:05, 15 May 2016

OCA — Sun, 15 May 2016 15:05:12 GMT

←Older revision		Revision as of 15:05, 15 May 2016
Line 3:		Line 3:
	The entry 5j5t is ON HOLD until Paper Publication		The entry 5j5t is ON HOLD until Paper Publication

-	Authors: ~~Silvian, L.F., Marcotte, D.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Silvian, L.F]]
-	[[Category: Marcotte, D]]

OCA: Protected "5j5t" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 01:30:37 GMT

Protected "5j5t" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:30, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5j5t is ON HOLD until Paper Publication Authors: Silvian, L.F., Marcotte, D. Description: Category: Unreleased Structures [[Category: Silvian,...

OCA — Wed, 11 May 2016 01:30:36 GMT

New page: '''Unreleased structure''' The entry 5j5t is ON HOLD until Paper Publication Authors: Silvian, L.F., Marcotte, D. Description: Category: Unreleased Structures [[Category: Silvian,...

New page

'''Unreleased structure'''

The entry 5j5t is ON HOLD until Paper Publication

Authors: Silvian, L.F., Marcotte, D.

Description:
[[Category: Unreleased Structures]]
[[Category: Silvian, L.F]]
[[Category: Marcotte, D]]