1s9j
From Proteopedia
(New page: 200px<br /> <applet load="1s9j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s9j, resolution 2.40Å" /> '''X-ray structure of ...) |
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| - | [[Image:1s9j.gif|left|200px]]<br /> | + | [[Image:1s9j.gif|left|200px]]<br /><applet load="1s9j" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1s9j" size=" | + | |
caption="1s9j, resolution 2.40Å" /> | caption="1s9j, resolution 2.40Å" /> | ||
'''X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP'''<br /> | '''X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | MEK1 and MEK2 are closely related, dual-specificity tyrosine/threonine | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1S9J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, ATP and BBM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1S9J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=BBM:'>BBM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S9J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chen, H.]] | [[Category: Chen, H.]] | ||
[[Category: Delaney, A.]] | [[Category: Delaney, A.]] | ||
| - | [[Category: Dudley, D | + | [[Category: Dudley, D T.]] |
| - | [[Category: Hasemann, C | + | [[Category: Hasemann, C A.]] |
[[Category: McConnell, P.]] | [[Category: McConnell, P.]] | ||
| - | [[Category: Ohren, J | + | [[Category: Ohren, J F.]] |
[[Category: Pavlovsky, A.]] | [[Category: Pavlovsky, A.]] | ||
[[Category: Sebolt-Leopold, J.]] | [[Category: Sebolt-Leopold, J.]] | ||
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[[Category: protein-protein interactions]] | [[Category: protein-protein interactions]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:14 2008'' |
Revision as of 12:59, 21 February 2008
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X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Overview
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.
About this Structure
1S9J is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:59:14 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Chen, H. | Delaney, A. | Dudley, D T. | Hasemann, C A. | McConnell, P. | Ohren, J F. | Pavlovsky, A. | Sebolt-Leopold, J. | Whitehead, C. | Yan, C. | ATP | BBM | MG | Protein kinase-ligand-mgatp complex | Protein-protein interactions
