5o7i - Revision history

OCA at 19:10, 29 November 2023

2023-11-29T19:10:32Z

← Older revision		Revision as of 19:10, 29 November 2023
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	<StructureSection load='5o7i' size='340' side='right'caption='[[5o7i]], [[Resolution\|resolution]] 2.38Å' scene=''>		<StructureSection load='5o7i' size='340' side='right'caption='[[5o7i]], [[Resolution\|resolution]] 2.38Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5o7i]] 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=5O7I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5O7I FirstGlance]. <br>		<table><tr><td colspan='2'>[[5o7i]] 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=5O7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O7I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N8:4-(2-bromanyl-6-fluoranyl-phenyl)carbonyl-~{N}-pyridin-3-yl-1~{H}-pyrrole-2-carboxamide'>9N8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 2.38Å</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK7, BMK1, ERK5, PRKM7 ([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=9N8:4-(2-bromanyl-6-fluoranyl-phenyl)carbonyl-~{N}-pyridin-3-yl-1~{H}-pyrrole-2-carboxamide'>9N8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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 Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=5o7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7i OCA], [https://pdbe.org/5o7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o7i RCSB], [https://www.ebi.ac.uk/pdbsum/5o7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7i 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=5o7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7i OCA], [~~http~~://pdbe.org/5o7i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5o7i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5o7i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7i ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>		[https://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]		*[[Mitogen-activated protein kinase 3D structures\|Mitogen-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Mitogen-activated protein kinase]]~~		[[Category: Heptinstall A]]
	[[Category: Heptinstall, A]]		[[Category: Myers S]]
	[[Category: Myers, S]]		[[Category: Tucker JA]]
	[[Category: Tucker~~, J A]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Pyrrole]]~~
	~~[[Category: Transferase~~]]

OCA at 07:19, 26 June 2019

2019-06-26T07:19:14Z

← Older revision		Revision as of 07:19, 26 June 2019
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>		[[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Extracellular regulated kinase 5 (ERK5) signalling has been implicated in driving a number of cellular phenotypes including endothelial cell angiogenesis and tumour cell motility. Novel ERK5 inhibitors were identified using high throughput screening, with a series of pyrrole-2-carboxamides substituted at the 4-position with an aroyl group being found to exhibit IC50 values in the micromolar range, but having no selectivity against p38alpha MAP kinase. Truncation of the N-substituent marginally enhanced potency ( approximately 3-fold) against ERK5, but importantly attenuated inhibition of p38alpha. Systematic variation of the substituents on the aroyl group led to the selective inhibitor 4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide (IC50 0.82muM for ERK5; IC50>120muM for p38alpha). The crystal structure (PDB 5O7I) of this compound in complex with ERK5 has been solved. This compound was orally bioavailable and inhibited bFGF-driven Matrigel plug angiogenesis and tumour xenograft growth. The selective ERK5 inhibitor described herein provides a lead for further development into a tool compound for more extensive studies seeking to examine the role of ERK5 signalling in cancer and other diseases.

			Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38alpha and BRD4.,Myers SM, Miller DC, Molyneux L, Arasta M, Bawn RH, Blackburn TJ, Cook SJ, Edwards N, Endicott JA, Golding BT, Griffin RJ, Hammonds T, Hardcastle IR, Harnor SJ, Heptinstall AB, Lochhead PA, Martin MP, Martin NC, Newell DR, Owen PJ, Pang LC, Reuillon T, Rigoreau LJM, Thomas HD, Tucker JA, Wang LZ, Wong AC, Noble MEM, Wedge SR, Cano C Eur J Med Chem. 2019 May 25;178:530-543. doi: 10.1016/j.ejmech.2019.05.057. PMID:31212132<ref>PMID:31212132</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5o7i" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 22:57, 5 June 2019

2019-06-05T22:57:38Z

← Older revision		Revision as of 22:57, 5 June 2019
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	==ERK5 in complex with a pyrrole inhibitor==		==ERK5 in complex with a pyrrole inhibitor==
	<StructureSection load='5o7i' size='340' side='right' caption='[[5o7i]], [[Resolution\|resolution]] 2.38Å' scene=''>		<StructureSection load='5o7i' size='340' side='right'caption='[[5o7i]], [[Resolution\|resolution]] 2.38Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5o7i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7I FirstGlance]. <br>		<table><tr><td colspan='2'>[[5o7i]] 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=5O7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N8:4-(2-bromanyl-6-fluoranyl-phenyl)carbonyl-~{N}-pyridin-3-yl-1~{H}-pyrrole-2-carboxamide'>9N8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N8:4-(2-bromanyl-6-fluoranyl-phenyl)carbonyl-~{N}-pyridin-3-yl-1~{H}-pyrrole-2-carboxamide'>9N8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAPK7, BMK1, ERK5, PRKM7 ([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 Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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 Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </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=5o7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7i OCA], [http://pdbe.org/5o7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o7i RCSB], [http://www.ebi.ac.uk/pdbsum/5o7i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7i 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=5o7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7i OCA], [http://pdbe.org/5o7i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o7i RCSB], [http://www.ebi.ac.uk/pdbsum/5o7i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7i ProSAT]</span></td></tr>
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>		[[http://www.uniprot.org/uniprot/MK07_HUMAN MK07_HUMAN]] Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction.<ref>PMID:9384584</ref> <ref>PMID:9790194</ref> <ref>PMID:11254654</ref> <ref>PMID:11278431</ref> <ref>PMID:22869143</ref>

			==See Also==
			*[[Mitogen-activated protein kinase\|Mitogen-activated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase]]		[[Category: Mitogen-activated protein kinase]]
	[[Category: Heptinstall, A]]		[[Category: Heptinstall, A]]

OCA at 05:37, 20 June 2018

2018-06-20T05:37:55Z

@@ Line 1: / Line 1: @@
-The entry 5o7i is ON HOLD  until Paper Publication
+==ERK5 in complex with a pyrrole inhibitor==
+<StructureSection load='5o7i' size='340' side='right' caption='[[5o7i]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5o7i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7I FirstGlance]. <br>
-Description:
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N8:4-(2-bromanyl-6-fluoranyl-phenyl)carbonyl-~{N}-pyridin-3-yl-1~{H}-pyrrole-2-carboxamide'>9N8</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span></td></tr>

OCA: Protected "5o7i" [edit=sysop:move=sysop]

2017-09-27T12:06:54Z

Protected "5o7i" [edit=sysop:move=sysop]

← Older revision	Revision as of 12:06, 27 September 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5o7i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2017-09-27T12:06:52Z

New page: '''Unreleased structure''' The entry 5o7i is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5o7i is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]