Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

3W8Q

Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 (MEK1)

Summary for 3W8Q
Entry DOI10.2210/pdb3w8q/pdb
DescriptorDual specificity mitogen-activated protein kinase kinase 1, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
Functional Keywordstransferase, nucleotide-binding, phosphorylation
Biological sourceHomo sapiens (human)
Cellular locationCytoplasm, cytoskeleton, microtubule organizing center, centrosome: Q02750
Total number of polymer chains1
Total formula weight39760.38
Authors
Nakae, S.,Kitamura, M.,Shirai, T.,Tada, T. (deposition date: 2013-03-20, release date: 2014-03-26, Last modification date: 2024-05-29)
Primary citationNakae, S.,Kitamura, M.,Fujiwara, D.,Sawa, M.,Shirai, T.,Fujii, I.,Tada, T.
Structure of mitogen-activated protein kinase kinase 1 in the DFG-out conformation.
Acta Crystallogr.,Sect.F, 77:459-464, 2021
Cited by
PubMed Abstract: Eukaryotic protein kinases contain an Asp-Phe-Gly (DFG) motif, the conformation of which is involved in controlling the catalytic activity, at the N-terminus of the activation segment. The motif can be switched between active-state (DFG-in) and inactive-state (DFG-out) conformations: however, the mechanism of conformational change is poorly understood, partly because there are few reports of the DFG-out conformation. Here, a novel crystal structure of nonphosphorylated human mitogen-activated protein kinase kinase 1 (MEK1; amino acids 38-381) complexed with ATP-γS is reported in which MEK1 adopts the DFG-out conformation. The crystal structure revealed that the structural elements (the αC helix and HRD motif) surrounding the active site are involved in the formation/stabilization of the DFG-out conformation. The ATP-γS molecule was bound to the canonical ATP-binding site in a different binding mode that has never been found in previously determined crystal structures of MEK1. This novel ATP-γS binding mode provides a starting point for the design of high-affinity inhibitors of nonphosphorylated inactive MEK1 that adopts the DFG-out conformation.
PubMed: 34866601
DOI: 10.1107/S2053230X21011687
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.2 Å)
Structure validation

227561

PDB entries from 2024-11-20

PDB statisticsPDBj update infoContact PDBjnumon