1s9i
From Proteopedia
(Difference between revisions)
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<StructureSection load='1s9i' size='340' side='right'caption='[[1s9i]], [[Resolution|resolution]] 3.20Å' scene=''> | <StructureSection load='1s9i' size='340' side='right'caption='[[1s9i]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1s9i]] is a 2 chain structure with sequence from [ | + | <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> |
| - | </td></tr><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><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | + | <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> | |
| - | + | <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> | |
| - | + | ||
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [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. |
== Function == | == Function == | ||
| - | [ | + | [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). |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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]. | </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]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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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| - | 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:15543157<ref>PMID:15543157</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1s9i" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | + | [[Category: Chen H]] | |
| - | [[Category: Chen | + | [[Category: Delaney A]] |
| - | [[Category: Delaney | + | [[Category: Dudley DT]] |
| - | [[Category: Dudley | + | [[Category: Hasemann CA]] |
| - | [[Category: Hasemann | + | [[Category: McConnell P]] |
| - | [[Category: McConnell | + | [[Category: Ohren JF]] |
| - | [[Category: Ohren | + | [[Category: Pavlovsky A]] |
| - | [[Category: Pavlovsky | + | [[Category: Sebolt-Leopold J]] |
| - | [[Category: Sebolt-Leopold | + | [[Category: Whitehead C]] |
| - | [[Category: Whitehead | + | [[Category: Yan C]] |
| - | [[Category: Yan | + | |
| - | + | ||
| - | + | ||
Current revision
X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP
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Categories: Homo sapiens | Large Structures | Chen H | Delaney A | Dudley DT | Hasemann CA | McConnell P | Ohren JF | Pavlovsky A | Sebolt-Leopold J | Whitehead C | Yan C
