3H2X

Crystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic Domain

3H2X の概要

• エントリーDOI: 10.2210/pdb3h2x/pdb
• 分子名称: Tyrosine-protein phosphatase non-receptor type 22, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: sh2-like fold, alternative splicing, cytoplasm, hydrolase, polymorphism, protein phosphatase, systemic lupus erythematosus
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q9Y2R2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36089.75

構造登録者

Tsai, S.J.,Sen, U. (登録日: 2009-04-14, 公開日: 2009-06-02, 最終更新日: 2024-10-30)

主引用文献

Tsai, S.J.,Sen, U.,Zhao, L.,Greenleaf, W.B.,Dasgupta, J.,Fiorillo, E.,Orru, V.,Bottini, N.,Chen, X.S.
Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .
Biochemistry, 48:4838-4845, 2009

PubMed Abstract: The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, recently emerged as an important risk factor and drug target for human autoimmunity. Here we solved the structure of the catalytic domain of LYP, which revealed noticeable differences with previously published structures. The active center with a semi-closed conformation binds a phosphate ion, which may represent an intermediate conformation after dephosphorylation of the substrate but before release of the phosphate product. The structure also revealed an unusual disulfide bond formed between the catalytic Cys and one of the two Cys residues nearby, which is not observed in previously determined structures. Our structural and mutagenesis data suggest that the disulfide bond may play a role in protecting the enzyme from irreversible oxidation. Surprisingly, we found that the two noncatalytic Cys around the active center exert an opposite yin-yang regulation on the catalytic Cys activity. These detailed structural and functional characterizations have provided new insights into autoregulatory mechanisms of LYP function.

PubMed: 19371084
DOI: 10.1021/bi900166y

実験手法

X-RAY DIFFRACTION (2.2 Å)