5VQ8

Crystal structure of human WT-KRAS in complex with GDP (EDTA soaked)

5VQ8 の概要

• エントリーDOI: 10.2210/pdb5vq8/pdb
• 関連するPDBエントリー: 5VP7 5VPI 5VPY 5VPZ 5VQ0 5VQ1 5VQ2 5VQ6
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Lipid-anchor ; Cytoplasmic side : P01116
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39722.70

構造登録者

Xu, S.,Long, B.,Boris, G.,Ni, S.,Kennedy, M.A. (登録日: 2017-05-08, 公開日: 2017-12-06, 最終更新日: 2024-03-13)

主引用文献

Xu, S.,Long, B.N.,Boris, G.H.,Chen, A.,Ni, S.,Kennedy, M.A.
Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras.
Acta Crystallogr D Struct Biol, 73:970-984, 2017

PubMed Abstract: K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPγS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP γ-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants.

PubMed: 29199977
DOI: 10.1107/S2059798317015418

実験手法

X-RAY DIFFRACTION (2.3 Å)