3ENM

The structure of the MAP2K MEK6 reveals an autoinhibitory dimer

3ENM の概要

• エントリーDOI: 10.2210/pdb3enm/pdb
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 6, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: mek6, autoinhibited dimer, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 147194.66

構造登録者

Min, X.,Akella, R.,He, H.,Humphreys, J.M.,Tsutakawa, S.,Lee, S.-J.,Tainer, J.A.,Cobb, M.H.,Goldsmith, E.J. (登録日: 2008-09-25, 公開日: 2009-03-03, 最終更新日: 2021-10-20)

主引用文献

Min, X.,Akella, R.,He, H.,Humphreys, J.M.,Tsutakawa, S.E.,Lee, S.J.,Tainer, J.A.,Cobb, M.H.,Goldsmith, E.J.
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer
Structure, 17:96-104, 2009

PubMed Abstract: MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/DeltaN/DD) has been solved at 2.3 angstroms resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/DeltaN/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare "arginine stack" between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.

PubMed: 19141286
DOI: 10.1016/j.str.2008.11.007

実験手法

X-RAY DIFFRACTION (2.35 Å)