6cqe - Revision history

OCA at 14:29, 13 March 2024

OCA — Wed, 13 Mar 2024 14:29:49 GMT

←Older revision		Revision as of 14:29, 13 March 2024
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	==Crystal structure of HPK1 kinase domain S171A mutant==		==Crystal structure of HPK1 kinase domain S171A mutant==
-	<StructureSection load='6cqe' size='340' side='right' caption='[[6cqe]], [[Resolution\|resolution]] 1.89Å' scene=''>	+	<StructureSection load='6cqe' size='340' side='right'caption='[[6cqe]], [[Resolution\|resolution]] 1.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cqe]] is a 2 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=6CQE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cqe]] is a 2 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=6CQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CQE FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>MAP4K1, HPK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</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]] 1.886Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=6cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqe OCA], [https://pdbe.org/6cqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cqe RCSB], [https://www.ebi.ac.uk/pdbsum/6cqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqe 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=6cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqe OCA], [~~http~~://pdbe.org/6cqe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6cqe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6cqe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqe ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN]] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>	+	[https://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Enhancement of antigen-specific T cell immunity has shown significant therapeutic benefit in infectious diseases and cancer. Hematopoietic progenitor kinase-1 (HPK1) is a negative-feedback regulator of T cell receptor signaling, which dampens T cell proliferation and effector function. A recent report showed that a catalytic dead mutant of HPK1 phenocopies augmented T cell responses observed in HPK1-knockout mice, indicating that kinase activity is critical for function. We evaluated active and inactive mutants and determined crystal structures of HPK1 kinase domain (HPK1-KD) in apo and ligand bound forms. In all structures HPK1-KD displays a rare domain-swapped dimer, in which the activation segment comprises a well-conserved dimer interface. Biophysical measurements show formation of dimer in solution. The activation segment adopts an alpha-helical structure which exhibits distinct orientations in active and inactive states. This face-to-face configuration suggests that the domain-swapped dimer may possess alternative selectivity for certain substrates of HPK1 under relevant cellular context.	+
-		+
-	Hematopoietic Progenitor Kinase-1 Structure in a Domain-Swapped Dimer.,Wu P, Sneeringer CJ, Pitts KE, Day ES, Chan BK, Wei B, Lehoux I, Mortara K, Li H, Wu J, Franke Y, Moffat JG, Grogan JL, Heffron TP, Wang W Structure. 2018 Nov 13. pii: S0969-2126(18)30386-1. doi:, 10.1016/j.str.2018.10.025. PMID:30503777<ref>PMID:30503777</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6cqe" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Non-specific serine/threonine protein kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Franke, Y]]	+	[[Category: Franke Y]]
-	[[Category: Lehoux, I]]	+	[[Category: Lehoux I]]
-	[[Category: Mortara, K]]	+	[[Category: Mortara K]]
-	[[Category: Wang, W]]	+	[[Category: Wang W]]
-	[[Category: Wu, P]]	+	[[Category: Wu P]]
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 12:30, 16 January 2019

OCA — Wed, 16 Jan 2019 12:30:06 GMT

←Older revision		Revision as of 12:30, 16 January 2019
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	<StructureSection load='6cqe' size='340' side='right' caption='[[6cqe]], [[Resolution\|resolution]] 1.89Å' scene=''>		<StructureSection load='6cqe' size='340' side='right' caption='[[6cqe]], [[Resolution\|resolution]] 1.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cqe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cqe]] is a 2 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=6CQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQE FirstGlance]. <br>
-	</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>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP4K1, HPK1 ([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='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=6cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqe OCA], [http://pdbe.org/6cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqe RCSB], [http://www.ebi.ac.uk/pdbsum/6cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqe 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=6cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqe OCA], [http://pdbe.org/6cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqe RCSB], [http://www.ebi.ac.uk/pdbsum/6cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqe ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Franke, Y]]		[[Category: Franke, Y]]

OCA at 08:18, 19 December 2018

OCA — Wed, 19 Dec 2018 08:18:11 GMT

←Older revision		Revision as of 08:18, 19 December 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6cqe is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of HPK1 kinase domain S171A mutant==
		+	<StructureSection load='6cqe' size='340' side='right' caption='[[6cqe]], [[Resolution\|resolution]] 1.89Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cqe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQE FirstGlance]. <br>
		+	</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=6cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqe OCA], [http://pdbe.org/6cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqe RCSB], [http://www.ebi.ac.uk/pdbsum/6cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqe ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M4K1_HUMAN M4K1_HUMAN]] Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate.<ref>PMID:24362026</ref> <ref>PMID:8824585</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Enhancement of antigen-specific T cell immunity has shown significant therapeutic benefit in infectious diseases and cancer. Hematopoietic progenitor kinase-1 (HPK1) is a negative-feedback regulator of T cell receptor signaling, which dampens T cell proliferation and effector function. A recent report showed that a catalytic dead mutant of HPK1 phenocopies augmented T cell responses observed in HPK1-knockout mice, indicating that kinase activity is critical for function. We evaluated active and inactive mutants and determined crystal structures of HPK1 kinase domain (HPK1-KD) in apo and ligand bound forms. In all structures HPK1-KD displays a rare domain-swapped dimer, in which the activation segment comprises a well-conserved dimer interface. Biophysical measurements show formation of dimer in solution. The activation segment adopts an alpha-helical structure which exhibits distinct orientations in active and inactive states. This face-to-face configuration suggests that the domain-swapped dimer may possess alternative selectivity for certain substrates of HPK1 under relevant cellular context.

-	~~Authors: Wu~~, P., ~~Lehoux~~, I., Mortara, K., ~~Franke~~, Y., ~~Wang~~, W.	+	Hematopoietic Progenitor Kinase-1 Structure in a Domain-Swapped Dimer.,Wu P, Sneeringer CJ, Pitts KE, Day ES, Chan BK, Wei B, Lehoux I, Mortara K, Li H, Wu J, Franke Y, Moffat JG, Grogan JL, Heffron TP, Wang W Structure. 2018 Nov 13. pii: S0969-2126(18)30386-1. doi:, 10.1016/j.str.2018.10.025. PMID:30503777<ref>PMID:30503777</ref>

-	~~Description: Crystal structure~~ of ~~HPK1 kinase domain S171A mutant~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Wang, W]]~~	+	<div class="pdbe-citations 6cqe" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Wu, P~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Franke, Y]]		[[Category: Franke, Y]]
-	[[Category: Mortara, K]]
	[[Category: Lehoux, I]]		[[Category: Lehoux, I]]
		+	[[Category: Mortara, K]]
		+	[[Category: Wang, W]]
		+	[[Category: Wu, P]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase]]

OCA at 06:09, 17 October 2018

OCA — Wed, 17 Oct 2018 06:09:08 GMT

←Older revision		Revision as of 06:09, 17 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6cqe is ON HOLD	+	The entry 6cqe is ON HOLD until Paper Publication

	Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W.		Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W.

OCA at 18:03, 19 September 2018

OCA — Wed, 19 Sep 2018 18:03:45 GMT

←Older revision		Revision as of 18:03, 19 September 2018
Line 5:		Line 5:
	Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W.		Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W.

-	Description: ~~M41-SM apo~~ structure	+	Description: Crystal structure of HPK1 kinase domain S171A mutant
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Wang, W]]		[[Category: Wang, W]]

OCA: Protected "6cqe" [edit=sysop:move=sysop]

OCA — Wed, 21 Mar 2018 06:14:47 GMT

Protected "6cqe" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:14, 21 March 2018

OCA: New page: '''Unreleased structure''' The entry 6cqe is ON HOLD Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W. Description: M41-SM apo structure [[Category: Unreleased Structures]...

OCA — Wed, 21 Mar 2018 06:14:46 GMT

New page: '''Unreleased structure''' The entry 6cqe is ON HOLD Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W. Description: M41-SM apo structure [[Category: Unreleased Structures]...

New page

'''Unreleased structure'''

The entry 6cqe is ON HOLD

Authors: Wu, P., Lehoux, I., Mortara, K., Franke, Y., Wang, W.

Description: M41-SM apo structure
[[Category: Unreleased Structures]]
[[Category: Wang, W]]
[[Category: Wu, P]]
[[Category: Franke, Y]]
[[Category: Mortara, K]]
[[Category: Lehoux, I]]