5W22
Crystal structure of human WT-KRAS in complex with GDP
5W22 の概要
エントリーDOI | 10.2210/pdb5w22/pdb |
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: 2017-06-05, 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 Cited by 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: 29199977DOI: 10.1107/S2059798317015418 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.762 Å) |
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