1YHV

Crystal Structure of PAK1 kinase domain with two point mutations (K299R, T423E)

1YHV の概要

• エントリーDOI: 10.2210/pdb1yhv/pdb
• 関連するPDBエントリー: 1YHW
• 分子名称: Serine/threonine-protein kinase PAK 1 (2 entities in total)
• 機能のキーワード: kinase; active conformation; activation loop; atp binding site, signaling protein, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q13153
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33301.24

構造登録者

Lei, M.,Robinson, M.A.,Harrison, S.C. (登録日: 2005-01-10, 公開日: 2005-05-24, 最終更新日: 2024-02-14)

主引用文献

Lei, M.,Robinson, M.A.,Harrison, S.C.
The Active Conformation of the PAK1 Kinase Domain
Structure, 13:769-778, 2005

PubMed Abstract: The p21-activated kinases (PAKs) participate in cytoskeletal control networks, downstream of Rho-family GTPases. A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces the latter into an inactive conformation, prevents phosphorylation of Thr423 in the activation loop, and promotes dimerization. We have now determined structures at 1.8 A resolution for the free PAK1 kinase domain, with a mutation in the active site that blocks enzymatic activity, and for the same domain with a "phosphomimetic" mutation in the activation loop. The two very similar structures show that even in the absence of a phosphorylated Thr423, the kinase has an essentially active conformation. When Cdc42 binds the regulatory region and dissociates the dimer, PAK1 will be in an "intermediate-active" state, with a capacity to phosphorylate itself or other substrates even prior to modification of its activation loop.

PubMed: 15893667
DOI: 10.1016/j.str.2005.03.007

実験手法

X-RAY DIFFRACTION (1.8 Å)