1S9I: X-Ray Structure Of The Human Mitogen-Activated Protein Kinase Kinase 2 (Mek2)in A Complex With Ligand And Mgatp

Citation:
Abstract
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.
PDB ID: 1S9IDownload
MMDB ID: 30282
PDB Deposition Date: 2004/2/4
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Similar Structures:
Biological Unit for 1S9I: dimeric; determined by author and by software (PISA)
Molecular Components in 1S9I
Label Count Molecule
Proteins (2 molecules)
2
Dual Specificity Mitogen-activated Protein Kinase Kinase 2(Gene symbol: MAP2K2)
Molecule annotation
Chemicals (6 molecules)
1
2
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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