2p55 - Revision history

OCA at 10:54, 30 August 2023

2023-08-30T10:54:34Z

←Older revision		Revision as of 10:54, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='2p55' size='340' side='right'caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2p55' size='340' side='right'caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P55 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2p55]] 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=2P55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P55 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1s9j\|1s9j]], [[1s9i\|1s9i]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP2K1, MEK1, PRKMK1 ([https://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'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [https://pdbe.org/2p55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [https://www.ebi.ac.uk/pdbsum/2p55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p55 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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [https://pdbe.org/2p55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [https://www.ebi.ac.uk/pdbsum/2p55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p55 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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.	+	[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 ==
-	[[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>	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase]]~~	+	[[Category: Ohren JF]]
-	[[Category: Ohren~~, J F~~]]	+	[[Category: Pavlovsky AG]]
-	[[Category: Pavlovsky~~, A G]]~~	+
-	~~[[Category: Ligand and mgatp]]~~	+
-	~~[[Category: Ligand co-complex]]~~	+
-	~~[[Category: Mitogen activated protein kinase kinase]]~~	+
-	~~[[Category: Non-competitive protein kinase inhibitor]]~~	+
-	~~[[Category: Protein kinase structure]]~~	+
-	~~[[Category: Signal transduction]]~~	+
-	~~[[Category: Ternary co-complex with kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 15:16, 17 June 2021

2021-06-17T15:16:20Z

←Older revision		Revision as of 15:16, 17 June 2021
Line 1:		Line 1:

	==X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP==		==X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP==
-	<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='2p55' size='340' side='right'caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2p55]] 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=2P55 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2P55 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P55 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1s9j\|1s9j]], [[1s9i\|1s9i]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MAP2K1, MEK1, PRKMK1 ([https://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'>[https://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [https://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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [~~http~~://pdbe.org/2p55 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2p55 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2p55 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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [https://pdbe.org/2p55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [https://www.ebi.ac.uk/pdbsum/2p55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p55 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 35:

	==See Also==		==See Also==
-	*[[Mitogen-activated protein kinase kinase\|Mitogen-activated protein kinase kinase]]	+	*[[Mitogen-activated protein kinase kinase 3D structures\|Mitogen-activated protein kinase kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 41:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Ohren, J F]]		[[Category: Ohren, J F]]

OCA at 06:45, 22 August 2018

2018-08-22T06:45:32Z

←Older revision		Revision as of 06:45, 22 August 2018
Line 1:		Line 1:
		+
	==X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP==		==X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP==
	<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>
Line 7:		Line 8:
	<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='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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://pdbe.org/2p55 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://pdbe.org/2p55 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p55 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p5/2p55_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p5/2p55_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2p55 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:14, 12 September 2015

2015-09-12T01:14:21Z

←Older revision		Revision as of 01:14, 12 September 2015
Line 2:		Line 2:
	<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P55 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2p55]] 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=2P55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P55 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</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 ~~Homo sapiens~~])</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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://pdbe.org/2p55 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 31:
	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 2p55" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Ohren, J F]]		[[Category: Ohren, J F]]

OCA at 16:10, 19 January 2015

2015-01-19T16:10:07Z

←Older revision		Revision as of 16:10, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P55 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P55 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</td></tr>
-	<tr><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 Homo sapiens])</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 Homo sapiens])</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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 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.
Line 40:		Line 40:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
-	[[Category: Ohren, J F.]]	+	[[Category: Ohren, J F]]
-	[[Category: Pavlovsky, A G.]]	+	[[Category: Pavlovsky, A G]]
	[[Category: Ligand and mgatp]]		[[Category: Ligand and mgatp]]
	[[Category: Ligand co-complex]]		[[Category: Ligand co-complex]]

OCA at 19:10, 30 September 2014

2014-09-30T19:10:30Z

←Older revision		Revision as of 19:10, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2p55\| PDB=2p55 \| SCENE= }}~~	+	==X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP==
-	===X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP===	+	<StructureSection load='2p55' size='340' side='right' caption='[[2p55]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~{{ABSTRACT_PUBMED_17880056}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[2p55]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P55 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MRA:2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE'>MRA</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1s9j\|1s9j]], [[1s9i\|1s9i]]</td></tr>
		+	<tr><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 Homo sapiens])</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=2p55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p55 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p55 RCSB], [http://www.ebi.ac.uk/pdbsum/2p55 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.		[[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>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p5/2p55_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by suppression of phosphorylated ERK substrate. Most notably, pyridone 27 was found to be more potent than 1 in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors.

-	~~==Function==~~	+	4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase.,Spicer JA, Rewcastle GW, Kaufman MD, Black SL, Plummer MS, Denny WA, Quin J 3rd, Shahripour AB, Barrett SD, Whitehead CE, Milbank JB, Ohren JF, Gowan RC, Omer C, Camp HS, Esmaeil N, Moore K, Sebolt-Leopold JS, Pryzbranowski S, Merriman RL, Ortwine DF, Warmus JS, Flamme CM, Pavlovsky AG, Tecle H J Med Chem. 2007 Oct 18;50(21):5090-102. Epub 2007 Sep 19. PMID:17880056<ref>PMID:17880056</ref>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[2p55]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Mitogen-activated protein kinase kinase\|Mitogen-activated protein kinase kinase]]		*[[Mitogen-activated protein kinase kinase\|Mitogen-activated protein kinase kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017880056</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]

OCA at 05:20, 25 March 2013

2013-03-25T05:20:01Z

←Older revision		Revision as of 05:20, 25 March 2013
Line 1:		Line 1:
-	[[Image:2p55.png\|left\|200px]]
-
	{{STRUCTURE_2p55\| PDB=2p55 \| SCENE= }}		{{STRUCTURE_2p55\| PDB=2p55 \| SCENE= }}
-
	===X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP===		===X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP===
		+	{{ABSTRACT_PUBMED_17880056}}

-	~~{{ABSTRACT_PUBMED_17880056}}~~	+	==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>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017880056</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017880056</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]

OCA at 22:04, 20 October 2012

2012-10-20T22:04:58Z

←Older revision		Revision as of 22:04, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[2p55]] is a 1 chain structure ~~of [[Mitogen-activated protein kinase kinase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA].	+	[[2p55]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA].

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

OCA: Protected "2p55" [edit=sysop:move=sysop]

2012-07-27T15:11:59Z

Protected "2p55" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:11, 27 July 2012

OCA at 15:11, 27 July 2012

2012-07-27T15:11:57Z

←Older revision		Revision as of 15:11, 27 July 2012
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-	{{Seed}}
	[[Image:2p55.png\|left\|200px]]		[[Image:2p55.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_2p55\| PDB=2p55 \| SCENE= }}		{{STRUCTURE_2p55\| PDB=2p55 \| SCENE= }}

	===X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP===		===X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_17880056}}, adds the Publication Abstract to the page
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	{{ABSTRACT_PUBMED_17880056}}		{{ABSTRACT_PUBMED_17880056}}

	==About this Structure==		==About this Structure==
-	~~2P55~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA].	+	[[2p55]] is a 1 chain structure of [[Mitogen-activated protein kinase kinase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P55 OCA].
		+
		+	==See Also==
		+	*[[Mitogen-activated protein kinase kinase\|Mitogen-activated protein kinase kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~17880056~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017880056</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
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	[[Category: Ternary co-complex with kinase]]		[[Category: Ternary co-complex with kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 08:59:15 2009''