6DZH

HRAS G13D bound to GDP (H13GDP)

6DZH の概要

• エントリーDOI: 10.2210/pdb6dzh/pdb
• 関連するPDBエントリー: 6E6C 6E6F 6E6G 6E6H 6E6P
• 分子名称: GTPase HRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: oncogene, ras, p21, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58553.00

構造登録者

Johnson, C.W.,Mattos, C. (登録日: 2018-07-04, 公開日: 2019-07-10, 最終更新日: 2023-10-11)

主引用文献

Johnson, C.W.,Lin, Y.J.,Reid, D.,Parker, J.,Pavlopoulos, S.,Dischinger, P.,Graveel, C.,Aguirre, A.J.,Steensma, M.,Haigis, K.M.,Mattos, C.
Isoform-Specific Destabilization of the Active Site Reveals a Molecular Mechanism of Intrinsic Activation of KRas G13D.
Cell Rep, 28:1538-1550.e7, 2019

PubMed Abstract: Ras GTPases are mutated at codons 12, 13, and 61, with different frequencies in KRas, HRas, and NRas and in a cancer-specific manner. The G13D mutant appears in 25% of KRas-driven colorectal cancers, while observed only rarely in HRas or NRas. Structures of Ras G13D in the three isoforms show an open active site, with adjustments to the D13 backbone torsion angles and with disconnected switch regions. KRas G13D has unique features that destabilize the nucleotide-binding pocket. In KRas G13D bound to GDP, A59 is placed in the Mg binding site, as in the HRas-SOS complex. Structure and biochemistry are consistent with an intermediate level of KRas G13D bound to GTP, relative to wild-type and KRas G12D, observed in genetically engineered mouse models. The results explain in part the elevated frequency of the G13D mutant in KRas over the other isoforms of Ras.

PubMed: 31390567
DOI: 10.1016/j.celrep.2019.07.026

実験手法

X-RAY DIFFRACTION (1.95 Å)