3W8Q
Structure of the Human Mitogen-Activated Protein Kinase Kinase 1 (MEK1)
Summary for 3W8Q
Entry DOI | 10.2210/pdb3w8q/pdb |
Descriptor | Dual specificity mitogen-activated protein kinase kinase 1, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total) |
Functional Keywords | transferase, nucleotide-binding, phosphorylation |
Biological source | Homo sapiens (human) |
Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: Q02750 |
Total number of polymer chains | 1 |
Total formula weight | 39760.38 |
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 citation | Nakae, 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: 34866601DOI: 10.1107/S2053230X21011687 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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