3zlx - Revision history

OCA at 10:41, 9 May 2024

OCA — Thu, 09 May 2024 10:41:02 GMT

←Older revision		Revision as of 10:41, 9 May 2024
Line 3:		Line 3:
	<StructureSection load='3zlx' size='340' side='right'caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3zlx' size='340' side='right'caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=5EZ:7-CHORO-6~~-[~~(3R)-PYRROLIDIN-3-YLMETHOXY~~]~~ISOQUINOLIN-1(2H)-ONE'>5EZ</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]] 2.2Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [https://pdbe.org/3zlx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [https://www.ebi.ac.uk/pdbsum/3zlx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlx 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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [https://pdbe.org/3zlx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [https://www.ebi.ac.uk/pdbsum/3zlx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlx 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Mitogen-activated protein kinase kinase]]~~	+	[[Category: Amaning K]]
-	[[Category: Amaning, K]]	+	[[Category: Andouche C]]
-	[[Category: Andouche, C]]	+	[[Category: Delorme C]]
-	[[Category: Delorme, C]]	+	[[Category: Halland N]]
-	[[Category: Halland, N]]	+	[[Category: Llopart S]]
-	[[Category: Llopart, S]]	+	[[Category: Lowinsky M]]
-	[[Category: Lowinsky, M]]	+	[[Category: Marcireau C]]
-	[[Category: Marcireau, C]]	+	[[Category: McCort G]]
-	[[Category: McCort, G]]	+	[[Category: Rak A]]
-	[[Category: Rak, A]]	+	[[Category: Steier V]]
-	[[Category: Steier, V]]	+	[[Category: Ugolini A]]
-	[[Category: Ugolini, A]]	+	[[Category: Vallee F]]
-	[[Category: Vallee, F]]	+	[[Category: Vougier S]]
-	[[Category: Vougier, S]]	+
-	~~[[Category: Transferase~~]]	+

OCA at 05:51, 10 August 2022

OCA — Wed, 10 Aug 2022 05:51:11 GMT

←Older revision		Revision as of 05:51, 10 August 2022
Line 3:		Line 3:
	<StructureSection load='3zlx' size='340' side='right'caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3zlx' size='340' side='right'caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</div></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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [~~http~~://pdbe.org/3zlx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3zlx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlx 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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [https://pdbe.org/3zlx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [https://www.ebi.ac.uk/pdbsum/3zlx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlx 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 ==
Line 24:		Line 24:

	==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/>

OCA at 07:24, 24 April 2019

OCA — Wed, 24 Apr 2019 07:24:09 GMT

←Older revision		Revision as of 07:24, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of MEK1 in complex with fragment 18==		==Crystal structure of MEK1 in complex with fragment 18==
-	<StructureSection load='3zlx' size='340' side='right' caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='3zlx' size='340' side='right'caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>		<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Amaning, K]]		[[Category: Amaning, K]]

OCA at 14:00, 11 August 2016

OCA — Thu, 11 Aug 2016 14:00:17 GMT

←Older revision		Revision as of 14:00, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of MEK1 in complex with fragment 18==		==Crystal structure of MEK1 in complex with fragment 18==
	<StructureSection load='3zlx' size='340' side='right' caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3zlx' size='340' side='right' caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [http://www.ebi.ac.uk/pdbsum/3zlx 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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [http://pdbe.org/3zlx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [http://www.ebi.ac.uk/pdbsum/3zlx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zlx 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 3zlx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
	[[Category: Amaning, K]]		[[Category: Amaning, K]]

OCA at 11:01, 4 January 2015

OCA — Sun, 04 Jan 2015 11:01:43 GMT

←Older revision		Revision as of 11:01, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_3zlx\| PDB=3zlx \| SCENE= }}~~	+	==Crystal structure of MEK1 in complex with fragment 18==
-	===Crystal structure of MEK1 in complex with fragment 18===	+	<StructureSection load='3zlx' size='340' side='right' caption='[[3zlx]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23648182}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3zlx]] 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=3ZLX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZLX FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EZ:7-CHORO-6-[(3R)-PYRROLIDIN-3-YLMETHOXY]ISOQUINOLIN-1(2H)-ONE'>5EZ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3zls\|3zls]], [[3zlw\|3zlw]], [[3zly\|3zly]], [[3zm4\|3zm4]]</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=3zlx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zlx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zlx RCSB], [http://www.ebi.ac.uk/pdbsum/3zlx 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report the analysis of an in-house fragment screening campaign for the oncology target MEK1. The application of virtual screening (VS) as a primary fragment screening approach, followed by biophysical validation using differential screening fluorimetry (DSF), with resultant binding mode determination by X-ray crystallography (X-ray), is presented as the most time and cost-effective combination of in silico and in vitro methods to identify fragments. We demonstrate the effectiveness of the VS-DSF workflow for the early identification of fragments to both 'jump-start' the drug discovery project and to complement biochemical screening data.

-	~~==Function==~~	+	The use of virtual screening and differential scanning fluorimetry for the rapid identification of fragments active against MEK1.,Amaning K, Lowinski M, Vallee F, Steier V, Marcireau C, Ugolini A, Delorme C, Foucalt F, McCort G, Derimay N, Andouche C, Vougier S, Llopart S, Halland N, Rak A Bioorg Med Chem Lett. 2013 Jun 15;23(12):3620-6. doi: 10.1016/j.bmcl.2013.04.003., Epub 2013 Apr 10. PMID:23648182<ref>PMID:23648182</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>
-	~~[[3zlx]] 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=3ZLX OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023648182</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Mitogen-activated protein kinase kinase\|Mitogen-activated protein kinase kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mitogen-activated protein kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase]]
-	[[Category: Amaning, K.]]	+	[[Category: Amaning, K]]
-	[[Category: Andouche, C.]]	+	[[Category: Andouche, C]]
-	[[Category: Delorme, C.]]	+	[[Category: Delorme, C]]
-	[[Category: Halland, N.]]	+	[[Category: Halland, N]]
-	[[Category: Llopart, S.]]	+	[[Category: Llopart, S]]
-	[[Category: Lowinsky, M.]]	+	[[Category: Lowinsky, M]]
-	[[Category: Marcireau, C.]]	+	[[Category: Marcireau, C]]
-	[[Category: McCort, G.]]	+	[[Category: McCort, G]]
-	[[Category: Rak, A.]]	+	[[Category: Rak, A]]
-	[[Category: Steier, V.]]	+	[[Category: Steier, V]]
-	[[Category: Ugolini, A.]]	+	[[Category: Ugolini, A]]
-	[[Category: Vallee, F.]]	+	[[Category: Vallee, F]]
-	[[Category: Vougier, S.]]	+	[[Category: Vougier, S]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 16:07, 19 June 2013

OCA — Wed, 19 Jun 2013 16:07:31 GMT

←Older revision		Revision as of 16:07, 19 June 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_3zlx\| PDB=3zlx \| SCENE= }}
		+	===Crystal structure of MEK1 in complex with fragment 18===
		+	{{ABSTRACT_PUBMED_23648182}}

-	~~The~~ entry ~~3zlx~~ is ~~ON HOLD until Paper Publication~~	+	==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.

-	~~Authors~~: ~~Amaning, K~~.~~, Lowinsky, M~~.~~, Vallee, F~~., ~~Steier, V~~.~~, Marcireau, C~~., ~~Ugolini~~, A., ~~Delorme~~, C., ~~McCort~~, ~~G., Andouche~~, C., ~~Vougier, S~~.~~, Llopart, S~~., ~~Halland~~, ~~N., Rak, A~~.	+	==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>

-	~~Description: Crystal~~ structure ~~of MEK1 in complex~~ with ~~fragment 18~~	+	==About this Structure==
		+	[[3zlx]] 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=3ZLX OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023648182</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Mitogen-activated protein kinase kinase]]
		+	[[Category: Amaning, K.]]
		+	[[Category: Andouche, C.]]
		+	[[Category: Delorme, C.]]
		+	[[Category: Halland, N.]]
		+	[[Category: Llopart, S.]]
		+	[[Category: Lowinsky, M.]]
		+	[[Category: Marcireau, C.]]
		+	[[Category: McCort, G.]]
		+	[[Category: Rak, A.]]
		+	[[Category: Steier, V.]]
		+	[[Category: Ugolini, A.]]
		+	[[Category: Vallee, F.]]
		+	[[Category: Vougier, S.]]
		+	[[Category: Transferase]]

OCA: Protected "3zlx" [edit=sysop:move=sysop]

OCA — Wed, 13 Feb 2013 09:53:33 GMT

Protected "3zlx" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:53, 13 February 2013

OCA: New page: '''Unreleased structure''' The entry 3zlx is ON HOLD until Paper Publication Authors: Amaning, K., Lowinsky, M., Vallee, F., Steier, V., Marcireau, C., Ugolini, A., Delorme, C., McCort,...

OCA — Wed, 13 Feb 2013 09:53:32 GMT

New page: '''Unreleased structure''' The entry 3zlx is ON HOLD until Paper Publication Authors: Amaning, K., Lowinsky, M., Vallee, F., Steier, V., Marcireau, C., Ugolini, A., Delorme, C., McCort,...

New page

'''Unreleased structure'''

The entry 3zlx is ON HOLD until Paper Publication

Authors: Amaning, K., Lowinsky, M., Vallee, F., Steier, V., Marcireau, C., Ugolini, A., Delorme, C., McCort, G., Andouche, C., Vougier, S., Llopart, S., Halland, N., Rak, A.

Description: Crystal structure of MEK1 in complex with fragment 18