7f2x - Revision history

OCA at 17:08, 29 November 2023

OCA — Wed, 29 Nov 2023 17:08:39 GMT

←Older revision		Revision as of 17:08, 29 November 2023
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	<StructureSection load='7f2x' size='340' side='right'caption='[[7f2x]], [[Resolution\|resolution]] 2.01Å' scene=''>		<StructureSection load='7f2x' size='340' side='right'caption='[[7f2x]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7f2x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F2X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7f2x]] 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=7F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F2X FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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]] 2.007Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=7f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f2x OCA], [https://pdbe.org/7f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f2x RCSB], [https://www.ebi.ac.uk/pdbsum/7f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f2x 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=7f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f2x OCA], [https://pdbe.org/7f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f2x RCSB], [https://www.ebi.ac.uk/pdbsum/7f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f2x ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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.
		+	== 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fujioka, Y]]	+	[[Category: Fujioka Y]]
-	[[Category: Noda~~, N N]]~~	+	[[Category: Noda NN]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 05:06, 10 August 2022

OCA — Wed, 10 Aug 2022 05:06:20 GMT

←Older revision		Revision as of 05:06, 10 August 2022
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	==Crystal structure of MEK1 C121S mutant==		==Crystal structure of MEK1 C121S mutant==
-	<StructureSection load='7f2x' size='340' side='right'caption='[[7f2x]]' scene=''>	+	<StructureSection load='7f2x' size='340' side='right'caption='[[7f2x]], [[Resolution\|resolution]] 2.01Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F2X FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7f2x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F2X FirstGlance]. <br>
-	</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=7f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f2x OCA], [https://pdbe.org/7f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f2x RCSB], [https://www.ebi.ac.uk/pdbsum/7f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f2x ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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=7f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f2x OCA], [https://pdbe.org/7f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f2x RCSB], [https://www.ebi.ac.uk/pdbsum/7f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f2x ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Point-mutations of MEK1, a central component of ERK signaling, are present in cancer and RASopathies, but their precise biological effects remain obscure. Here, we report a mutant MEK1 structure that uncovers the mechanisms underlying abnormal activities of cancer- and RASopathy-associated MEK1 mutants. These two classes of MEK1 mutations differentially impact on spatiotemporal dynamics of ERK signaling, cellular transcriptional programs, gene expression profiles, and consequent biological outcomes. By making use of such distinct characteristics of the MEK1 mutants, we identified cancer- and RASopathy-signature genes that may serve as diagnostic markers or therapeutic targets for these diseases. In particular, two AKT-inhibitor molecules, PHLDA1 and 2, are simultaneously upregulated by oncogenic ERK signaling, and mediate cancer-specific ERK-AKT crosstalk. The combined expression of PHLDA1/2 is critical to confer resistance to ERK pathway-targeted therapeutics on cancer cells. Finally, we propose a therapeutic strategy to overcome this drug resistance. Our data provide vital insights into the etiology, diagnosis, and therapeutic strategy of cancers and RASopathies.
		+
		+	Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer.,Kubota Y, Fujioka Y, Patil A, Takagi Y, Matsubara D, Iijima M, Momose I, Naka R, Nakai K, Noda NN, Takekawa M Nat Commun. 2022 Jul 13;13(1):4063. doi: 10.1038/s41467-022-31690-w. PMID:35831322<ref>PMID:35831322</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7f2x" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fujioka Y]]	+	[[Category: Fujioka, Y]]
-	[[Category: Noda NN]]	+	[[Category: Noda, N N]]
		+	[[Category: Kinase]]
		+	[[Category: Signaling protein]]

OCA at 09:42, 22 June 2022

OCA — Wed, 22 Jun 2022 09:42:55 GMT

←Older revision		Revision as of 09:42, 22 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7f2x ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of MEK1 C121S mutant==
-		+	<StructureSection load='7f2x' size='340' side='right'caption='[[7f2x]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F2X FirstGlance]. <br>
-	~~Description~~:	+	</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=7f2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f2x OCA], [https://pdbe.org/7f2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f2x RCSB], [https://www.ebi.ac.uk/pdbsum/7f2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f2x ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Fujioka Y]]
		+	[[Category: Noda NN]]

OCA at 08:39, 7 July 2021

OCA — Wed, 07 Jul 2021 08:39:09 GMT

←Older revision		Revision as of 08:39, 7 July 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7f2x is ON HOLD	+	The entry 7f2x is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7f2x" [edit=sysop:move=sysop]

OCA — Fri, 25 Jun 2021 06:05:41 GMT

Protected "7f2x" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:05, 25 June 2021

OCA: New page: '''Unreleased structure''' The entry 7f2x is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Fri, 25 Jun 2021 06:05:40 GMT

New page: '''Unreleased structure''' The entry 7f2x is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7f2x is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]