6e2m - Revision history

OCA at 08:37, 17 October 2018

OCA — Wed, 17 Oct 2018 08:37:43 GMT

←Older revision		Revision as of 08:37, 17 October 2018
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	<StructureSection load='6e2m' size='340' side='right' caption='[[6e2m]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='6e2m' size='340' side='right' caption='[[6e2m]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e2m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E2M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e2m]] 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=6E2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E2M FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KK7:N-[3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl]pyridine-2-carboxamide'>KK7</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KK7:N-[3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl]pyridine-2-carboxamide'>KK7</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">MAP3K5, ASK1, MAPKKK5, MEKK5 ([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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=6e2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e2m OCA], [http://pdbe.org/6e2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e2m RCSB], [http://www.ebi.ac.uk/pdbsum/6e2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e2m 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=6e2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e2m OCA], [http://pdbe.org/6e2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e2m RCSB], [http://www.ebi.ac.uk/pdbsum/6e2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e2m ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Lansdon, E B]]		[[Category: Lansdon, E B]]

OCA at 19:52, 19 September 2018

OCA — Wed, 19 Sep 2018 19:52:00 GMT

←Older revision		Revision as of 19:52, 19 September 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6e2m is ~~ON HOLD~~	+	==ASK1 kinase domain complex with inhibitor==
		+	<StructureSection load='6e2m' size='340' side='right' caption='[[6e2m]], [[Resolution\|resolution]] 2.25Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6e2m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E2M FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KK7:N-[3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl]pyridine-2-carboxamide'>KK7</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/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </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=6e2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e2m OCA], [http://pdbe.org/6e2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e2m RCSB], [http://www.ebi.ac.uk/pdbsum/6e2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e2m ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K5_HUMAN M3K5_HUMAN]] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).<ref>PMID:8940179</ref> <ref>PMID:8974401</ref> <ref>PMID:9564042</ref> <ref>PMID:9774977</ref> <ref>PMID:10411906</ref> <ref>PMID:10849426</ref> <ref>PMID:10688666</ref> <ref>PMID:11689443</ref> <ref>PMID:11029458</ref> <ref>PMID:11154276</ref> <ref>PMID:14749717</ref> <ref>PMID:11920685</ref> <ref>PMID:12697749</ref> <ref>PMID:15023544</ref> <ref>PMID:14688258</ref> <ref>PMID:16129676</ref> <ref>PMID:17220297</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Oxidative stress is an underlying component of acute and chronic kidney disease. Apoptosis signal-regulating kinase 1 (ASK1) is a widely expressed redox-sensitive serine threonine kinase that activates p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase kinases, and induces apoptotic, inflammatory, and fibrotic signaling in settings of oxidative stress. We describe the discovery and characterization of a potent and selective small-molecule inhibitor of ASK1, GS-444217, and demonstrate the therapeutic potential of ASK1 inhibition to reduce kidney injury and fibrosis. Activation of the ASK1 pathway in glomerular and tubular compartments was confirmed in renal biopsies from patients with diabetic kidney disease (DKD) and was decreased by GS-444217 in several rodent models of kidney injury and fibrosis that collectively represented the hallmarks of DKD pathology. Treatment with GS-444217 reduced progressive inflammation and fibrosis in the kidney and halted glomerular filtration rate decline. Combination of GS-444217 with enalapril, an angiotensin-converting enzyme inhibitor, led to a greater reduction in proteinuria and regression of glomerulosclerosis. These results identify ASK1 as an important target for renal disease and support the clinical development of an ASK1 inhibitor for the treatment of DKD.

-	~~Authors:~~ Lansdon, E.B.	+	ASK1 contributes to fibrosis and dysfunction in models of kidney disease.,Liles JT, Corkey BK, Notte GT, Budas GR, Lansdon EB, Hinojosa-Kirschenbaum F, Badal SS, Lee M, Schultz BE, Wise S, Pendem S, Graupe M, Castonguay L, Koch KA, Wong MH, Papalia GA, French DM, Sullivan T, Huntzicker EG, Ma FY, Nikolic-Paterson DJ, Altuhaifi T, Yang H, Fogo AB, Breckenridge DG J Clin Invest. 2018 Sep 4. pii: 99768. doi: 10.1172/JCI99768. PMID:30024858<ref>PMID:30024858</ref>

-	~~Description~~: ~~ASK1 kinase domain complex with inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Lansdon, E.B]]	+	<div class="pdbe-citations 6e2m" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
		+	[[Category: Lansdon, E B]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-inhibitor complex]]

OCA: Protected "6e2m" [edit=sysop:move=sysop]

OCA — Wed, 18 Jul 2018 05:43:17 GMT

Protected "6e2m" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6e2m is ON HOLD Authors: Lansdon, E.B. Description: ASK1 kinase domain complex with inhibitor Category: Unreleased Structures [[Category: Lansd...

OCA — Wed, 18 Jul 2018 05:43:16 GMT

New page: '''Unreleased structure''' The entry 6e2m is ON HOLD Authors: Lansdon, E.B. Description: ASK1 kinase domain complex with inhibitor Category: Unreleased Structures [[Category: Lansd...

New page

'''Unreleased structure'''

The entry 6e2m is ON HOLD

Authors: Lansdon, E.B.

Description: ASK1 kinase domain complex with inhibitor
[[Category: Unreleased Structures]]
[[Category: Lansdon, E.B]]