5IBS

Structure of E76Q, a Cancer-Associated Mutation of the Oncogenic Phosphatase SHP2

5IBS の概要

• エントリーDOI: 10.2210/pdb5ibs/pdb
• 関連するPDBエントリー: 5IBM
• 分子名称: Tyrosine-protein phosphatase non-receptor type 11 (2 entities in total)
• 機能のキーワード: tyrosine phosphatase shp2, tyrosine-protein phosphatase non-receptor type 11, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q06124
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120668.10

構造登録者

Blacklow, S.C.,Stams, T.,Fodor, M.,LaRochelle, J.R. (登録日: 2016-02-22, 公開日: 2016-04-13, 最終更新日: 2023-09-27)

主引用文献

LaRochelle, J.R.,Fodor, M.,Xu, X.,Durzynska, I.,Fan, L.,Stams, T.,Chan, H.M.,LaMarche, M.J.,Chopra, R.,Wang, P.,Fortin, P.D.,Acker, M.G.,Blacklow, S.C.
Structural and Functional Consequences of Three Cancer-Associated Mutations of the Oncogenic Phosphatase SHP2.
Biochemistry, 55:2269-2277, 2016

PubMed Abstract: The proto-oncogene PTPN11 encodes a cytoplasmic protein tyrosine phosphatase, SHP2, which is required for normal development and sustained activation of the Ras-MAPK signaling pathway. Germline mutations in SHP2 cause developmental disorders, and somatic mutations have been identified in childhood and adult cancers and drive leukemia in mice. Despite our knowledge of the PTPN11 variations associated with pathology, the structural and functional consequences of many disease-associated mutants remain poorly understood. Here, we combine X-ray crystallography, small-angle X-ray scattering, and biochemistry to elucidate structural and mechanistic features of three cancer-associated SHP2 variants harboring single point mutations within the N-SH2:PTP interdomain autoinhibitory interface. Our findings directly compare the impact of each mutation on autoinhibition of the phosphatase and advance the development of structure-guided and mutation-specific SHP2 therapies.

PubMed: 27030275
DOI: 10.1021/acs.biochem.5b01287

実験手法

X-RAY DIFFRACTION (2.32 Å)