Crystal structures of the state 1 conformations of the GTP‐bound H‐Ras protein and its oncogenic G12V and Q61L mutants | Zendy

Muraoka Shin | Zendy; Shima Fumi | Zendy; Araki Mitsugu | Zendy; Inoue Tomoko | Zendy; Yoshimoto Akiko | Zendy; Ijiri Yuichi | Zendy; Seki Nobuaki | Zendy; Tamura Atsuo | Zendy; Kumasaka Takashi | Zendy; Yamamoto Masaki | Zendy; Kataoka Tohru | Zendy

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Crystal structures of the state 1 conformations of the GTP‐bound H‐Ras protein and its oncogenic G12V and Q61L mutants

Author(s) -

Muraoka Shin,

Shima Fumi,

Araki Mitsugu,

Inoue Tomoko,

Yoshimoto Akiko,

Ijiri Yuichi,

Seki Nobuaki,

Tamura Atsuo,

Kumasaka Takashi,

Yamamoto Masaki,

Kataoka Tohru

Publication year - 2012

Publication title -

febs letters

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.593

H-Index - 257

eISSN - 1873-3468

pISSN - 0014-5793

DOI - 10.1016/j.febslet.2012.04.058

Subject(s) - gtp' , gtpase , mutant , chemistry , molecular switch , wild type , small gtpase , crystal structure , crystallography , stereochemistry , biophysics , enzyme , biochemistry , molecule , biology , gene , signal transduction , organic chemistry

GTP‐bound Ras adopts two interconverting conformations, “inactive” state 1 and “active” state 2. However, the tertiary structure of wild‐type (WT) state 1 remains unsolved. Here we solve the state 1 crystal structures of H‐Ras WT together with its oncogenic G12V and Q61L mutants. They assume open structures characterized by impaired interactions of both Thr‐35 in switch I and Gly‐60 in switch II with the γ‐phosphate of GTP and possess two surface pockets of mutually different shapes unseen in state 2, a potential target for selective inhibitor development. Furthermore, they provide a structural basis for the low GTPase activity of state 1.

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