1s9i

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[[Image:1s9i.gif|left|200px]]
 
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{{Structure
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==X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP==
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|PDB= 1s9i |SIZE=350|CAPTION= <scene name='initialview01'>1s9i</scene>, resolution 3.20&Aring;
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<StructureSection load='1s9i' size='340' side='right'caption='[[1s9i]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=5EA:5-{3,4-DIFLUORO-2-[(2-FLUORO-4-IODOPHENYL)AMINO]PHENYL}-N-(2-MORPHOLIN-4-YLETHYL)-1,3,4-OXADIAZOL-2-AMINE'>5EA</scene>, <scene name='pdbligand=ATP:ADENOSINE-5&#39;-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
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<table><tr><td colspan='2'>[[1s9i]] is a 2 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=1S9I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S9I FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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|GENE= MAP2K2, PRKMK2, MEK2, MKK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EA:5-{3,4-DIFLUORO-2-[(2-FLUORO-4-IODOPHENYL)AMINO]PHENYL}-N-(2-MORPHOLIN-4-YLETHYL)-1,3,4-OXADIAZOL-2-AMINE'>5EA</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s9i OCA], [https://pdbe.org/1s9i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s9i RCSB], [https://www.ebi.ac.uk/pdbsum/1s9i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s9i ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1s9j|1S9J]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s9i OCA], [http://www.ebi.ac.uk/pdbsum/1s9i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s9i RCSB]</span>
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== Disease ==
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}}
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[https://www.uniprot.org/uniprot/MP2K2_HUMAN MP2K2_HUMAN] Defects in MAP2K2 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.
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== Function ==
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[https://www.uniprot.org/uniprot/MP2K2_HUMAN MP2K2_HUMAN] Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s9/1s9i_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1s9i ConSurf].
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<div style="clear:both"></div>
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'''X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP'''
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==See Also==
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*[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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MEK1 and MEK2 are closely related, dual-specificity tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. Approximately 30% of all human cancers have a constitutively activated MAPK pathway, and constitutive activation of MEK1 results in cellular transformation. Here we present the X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 A and 3.2 A, respectively. The structures reveal that MEK1 and MEK2 each have a unique inhibitor-binding pocket adjacent to the MgATP-binding site. The presence of the potent inhibitor induces several conformational changes in the unphosphorylated MEK1 and MEK2 enzymes that lock them into a closed but catalytically inactive species. Thus, the structures reported here reveal a novel, noncompetitive mechanism for protein kinase inhibition.
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==About this Structure==
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1S9I is a [[Single protein]] 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=1S9I OCA].
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==Reference==
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Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition., Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, Yan C, McConnell P, Spessard C, Banotai C, Mueller WT, Delaney A, Omer C, Sebolt-Leopold J, Dudley DT, Leung IK, Flamme C, Warmus J, Kaufman M, Barrett S, Tecle H, Hasemann CA, Nat Struct Mol Biol. 2004 Dec;11(12):1192-7. Epub 2004 Nov 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15543157 15543157]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Chen H]]
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[[Category: Chen, H.]]
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[[Category: Delaney A]]
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[[Category: Delaney, A.]]
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[[Category: Dudley DT]]
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[[Category: Dudley, D T.]]
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[[Category: Hasemann CA]]
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[[Category: Hasemann, C A.]]
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[[Category: McConnell P]]
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[[Category: McConnell, P.]]
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[[Category: Ohren JF]]
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[[Category: Ohren, J F.]]
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[[Category: Pavlovsky A]]
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[[Category: Pavlovsky, A.]]
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[[Category: Sebolt-Leopold J]]
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[[Category: Sebolt-Leopold, J.]]
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[[Category: Whitehead C]]
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[[Category: Whitehead, C.]]
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[[Category: Yan C]]
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[[Category: Yan, C.]]
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[[Category: protein kinase-ligand-mgatp complex]]
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[[Category: protein-protein interaction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:39:04 2008''
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Current revision

X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP

PDB ID 1s9i

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