4u80 - Revision history

OCA at 07:25, 27 September 2023

2023-09-27T07:25:57Z

←Older revision		Revision as of 07:25, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4u80]] 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=4U80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U80 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4u80]] 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=4U80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U80 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.8Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [https://pdbe.org/4u80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [https://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [https://pdbe.org/4u80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [https://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:07, 22 March 2023

2023-03-22T08:07:37Z

←Older revision		Revision as of 08:07, 22 March 2023
Line 1:		Line 1:

	==MEK 1 kinase bound to G799==		==MEK 1 kinase bound to G799==
-	<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='4u80' size='340' side='right'caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4u80]] 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=4U80 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4U80 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4u80]] 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=4U80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U80 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [https://pdbe.org/4u80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [https://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP2K1, MEK1, PRKMK1 ([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 Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [~~http~~://pdbe.org/4u80 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[~~http~~://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.	+	[https://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN] Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.<ref>PMID:14737111</ref> <ref>PMID:17101779</ref>	+	[https://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.<ref>PMID:14737111</ref> <ref>PMID:17101779</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4u80" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4u80" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase kinase 3D structures\|Mitogen-activated protein kinase kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Mitogen-activated protein kinase kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Robarge~~, K D~~]]	+	[[Category: Robarge KD]]
-	[[Category: Ultsch~~, M H~~]]	+	[[Category: Ultsch MH]]
-	[[Category: Weismann, C]]	+	[[Category: Weismann C]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 22:39, 15 November 2017

2017-11-15T22:39:45Z

←Older revision		Revision as of 22:39, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4u80]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U80 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4u80]] 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=4U80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U80 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP2K1, MEK1, PRKMK1 ([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 Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://pdbe.org/4u80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://pdbe.org/4u80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Robarge, K D]]		[[Category: Robarge, K D]]
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	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Kinase]]		[[Category: Kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 15:03, 11 August 2016

2016-08-11T15:03:35Z

←Older revision		Revision as of 15:03, 11 August 2016
Line 1:		Line 1:
		+
	==MEK 1 kinase bound to G799==		==MEK 1 kinase bound to G799==
	<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</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 Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum]</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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://pdbe.org/4u80 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u80 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4u80" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:53, 20 January 2015

2015-01-20T08:53:59Z

←Older revision		Revision as of 08:53, 20 January 2015
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
-	[[Category: Robarge, K D.]]	+	[[Category: Robarge, K D]]
-	[[Category: Ultsch, M H.]]	+	[[Category: Ultsch, M H]]
-	[[Category: Weismann, C.]]	+	[[Category: Weismann, C]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Kinase]]		[[Category: Kinase]]

OCA at 05:34, 8 October 2014

2014-10-08T05:34:33Z

←Older revision		Revision as of 05:34, 8 October 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4u80]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U80 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4u80]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U80 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum]</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=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.		[[http://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.

OCA at 10:18, 24 September 2014

2014-09-24T10:18:40Z

←Older revision		Revision as of 10:18, 24 September 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==MEK 1 kinase bound to G799==
		+	<StructureSection load='4u80' size='340' side='right' caption='[[4u80]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4u80]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U80 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U80 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EX:3-[(4-CYCLOPROPYL-2-FLUOROPHENYL)AMINO]-N-(2-HYDROXYETHOXY)FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>3EX</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[4u7z\|4u7z]], [[4u81\|4u81]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u80 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u80 RCSB], [http://www.ebi.ac.uk/pdbsum/4u80 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MP2K1_HUMAN MP2K1_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.<ref>PMID:14737111</ref> <ref>PMID:17101779</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Use of the tools of SBDD including crystallography led to the discovery of novel and potent 6,5 heterobicyclic MEKi's [J. Med. Chem.2012, 55, 4594]. The core change from a 5,6 heterobicycle to a 6,5 heterobicycle was driven by the desire for increased structural diversity and aided by the co-crystal structure of G-925 [J. Med. Chem.2012, 55, 4594]. The key design feature was the shift of the attachment of the five-membered heterocyclic ring towards the B ring while maintaining the key hydroxamate and anilino pharamcophoric elements in a remarkably similar position as in G-925. From modelling, changing the connection point of the five membered ring heterocycle placed the H-bond accepting nitrogen within a good distance and angle to the Ser212 [J. Med. Chem.2012, 55, 4594]. The resulting novel 6,5 benzoisothiazole MEKi G-155 exhibited improved potency versus aza-benzofurans G-925 and G-963 but was a potent inhibitor of cytochrome P450's 2C9 and 2C19. Lowering the logD by switching to the more polar imidazo[1,5-a] pyridine core significantly diminished 2C9/2C19 inhibition while retaining potency. The imidazo[1,5-a] pyridine G-868 exhibited increased potency versus the starting point for this work (aza-benzofuran G-925) leading to deprioritization of the azabenzofurans. The 6,5-imidazo[1,5-a] pyridine scaffold was further diversified by incorporating a nitrogen at the 7 position to give the imidazo[1,5-a] pyrazine scaffold. The introduction of the C7 nitrogen was driven by the desire to improve metabolic stability by blocking metabolism at the C7 and C8 positions (particularly the HLM stability). It was found that improving on G-868 (later renamed GDC-0623) required combining C7 nitrogen with a diol hydroxamate to give G-479. G-479 with polarity distributed throughout the molecule was improved over G-868 in many aspects.

-	~~The entry 4u80 is ON HOLD~~	+	Structure based design of novel 6,5 heterobicyclic mitogen-activated protein kinase kinase (MEK) inhibitors leading to the discovery of imidazo[1,5-a] pyrazine G-479.,Robarge KD, Lee W, Eigenbrot C, Ultsch M, Wiesmann C, Heald R, Price S, Hewitt J, Jackson P, Savy P, Burton B, Choo EF, Pang J, Boggs J, Yang A, Yang X, Baumgardner M Bioorg Med Chem Lett. 2014 Aug 15. pii: S0960-894X(14)00839-7. doi:, 10.1016/j.bmcl.2014.08.008. PMID:25193232<ref>PMID:25193232</ref>

-	~~Authors: Ultsch~~, M.H., Robarge, K., Weismann, C.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~MEK 1 kinase bound to G799~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase]]
		+	[[Category: Robarge, K D.]]
		+	[[Category: Ultsch, M H.]]
		+	[[Category: Weismann, C.]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]

OCA: Protected "4u80" [edit=sysop:move=sysop]

2014-08-07T01:34:37Z

Protected "4u80" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:34, 7 August 2014

OCA: New page: '''Unreleased structure''' The entry 4u80 is ON HOLD Authors: Ultsch, M.H., Robarge, K., Weismann, C. Description: MEK 1 kinase bound to G799

2014-08-07T01:34:36Z

New page: '''Unreleased structure''' The entry 4u80 is ON HOLD Authors: Ultsch, M.H., Robarge, K., Weismann, C. Description: MEK 1 kinase bound to G799

New page

'''Unreleased structure'''

The entry 4u80 is ON HOLD

Authors: Ultsch, M.H., Robarge, K., Weismann, C.

Description: MEK 1 kinase bound to G799