1OO3

P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase

1OO3 の概要

• エントリーDOI: 10.2210/pdb1oo3/pdb
• 関連するPDBエントリー: 1OO4
• 分子名称: Phosphatidylinositol 3-kinase regulatory alpha subunit (1 entity in total)
• 機能のキーワード: src homology 2 domain p85 regulatory subunit mutant, protein binding
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12860.35

構造登録者

Guenther, U.L.,Weyrauch, B.,Schaffhausen, B. (登録日: 2003-03-03, 公開日: 2003-03-25, 最終更新日: 2024-05-29)

主引用文献

Guenther, U.L.,Weyrauch, B.,Zhang, X.,Schaffhausen, B.
Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity
Biochemistry, 42:11120-11127, 2003

PubMed Abstract: Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K). The P395S mutant exhibits a specificity for phosphopeptide binding different from that of the wild-type SH2. The P395S mutant has an increased affinity for the platelet-derived growth factor receptor (PDGFr) compared to polyomavirus middle T antigen (MT). Solution structures of the P395S mutant of the p85 N-SH2 alone and complexed to a PDGFr phosphopeptide were determined to explain the change in specificity. Chemical shift perturbations caused by different peptides were compared for mutant and wild-type structures. The results show that the single P395S mutation has broad effects on the structure. Furthermore, they provide a rationale for the observed changes in binding preference.

PubMed: 14503862
DOI: 10.1021/bi034353x

実験手法

SOLUTION NMR