6UNA

Crystal structure of inactive p38gamma

6UNA の概要

• エントリーDOI: 10.2210/pdb6una/pdb
• 分子名称: Mitogen-activated protein kinase 12, GLYCEROL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mapk, mitogen activated protein kinase, p38 gamma, mapk12, inactive kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83235.31

構造登録者

Aoto, P.C.,Stanfield, R.L.,Wilson, I.A.,Dyson, H.J.,Wright, P.E. (登録日: 2019-10-11, 公開日: 2019-12-18, 最終更新日: 2023-10-11)

主引用文献

Aoto, P.C.,Stanfield, R.L.,Wilson, I.A.,Dyson, H.J.,Wright, P.E.
A Dynamic Switch in Inactive p38 gamma Leads to an Excited State on the Pathway to an Active Kinase.
Biochemistry, 58:5160-5172, 2019

PubMed Abstract: The inactive state of mitogen-activated protein kinases (MAPKs) adopts an open conformation while the active state exists in a compact form stabilized by phosphorylation. In the active state, eukaryotic kinases undergo breathing motions related to substrate binding and product release that have not previously been detected in the inactive state. However, docking interactions of partner proteins with inactive MAPK kinases exhibit allostery in binding of activating kinases. Interactions at a site distant from the activation loop are coupled to the configuration of the activation loop, suggesting that the inactive state may also undergo concerted dynamics. X-ray crystallographic studies of nonphosphorylated, inactive p38γ reveal differences in domain orientations and active site structure in the two molecules in the asymmetric unit. One molecule resembles an inactive kinase with an open active site. The second molecule has a rotation of the N-lobe that leads to partial compaction of the active site, resulting in a conformation that is intermediate between the inactive open state and the fully closed state of the activated kinase. Although the compact state of apo p38γ displays several of the features of the activated enzyme, it remains catalytically inert. In solution, the kinase fluctuates on a millisecond time scale between the open ground state and a weakly populated excited state that is similar in structure to the compact state observed in the crystal. The nuclear magnetic resonance and crystal structure data imply that interconversion between the open and compact states involves a molecular switch associated with the DFG loop.

PubMed: 31794659
DOI: 10.1021/acs.biochem.9b00932

実験手法

X-RAY DIFFRACTION (2.554 Å)