1A5Y

PROTEIN TYROSINE PHOSPHATASE 1B CYSTEINYL-PHOSPHATE INTERMEDIATE

1A5Y の概要

• エントリーDOI: 10.2210/pdb1a5y/pdb
• 分子名称: PROTEIN TYROSINE PHOSPHATASE 1B (2 entities in total)
• 機能のキーワード: hydrolase, dephosphorylation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P18031
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38469.81

構造登録者

Pannifer, A.D.P.,Flint, A.J.,Tonks, N.K.,Barford, D. (登録日: 1998-02-19, 公開日: 1998-06-17, 最終更新日: 2024-10-23)

主引用文献

Pannifer, A.D.,Flint, A.J.,Tonks, N.K.,Barford, D.
Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by x-ray crystallography.
J.Biol.Chem., 273:10454-10462, 1998

PubMed Abstract: Protein-tyrosine phosphatases (PTPs) are signal transduction enzymes that catalyze the dephosphorylation of phosphotyrosine residues via the formation of a transient cysteinyl-phosphate intermediate. The mechanism of hydrolysis of this intermediate has been examined by generating a Gln-262 --> Ala mutant of PTP1B, which allows the accumulation and trapping of the intermediate within a PTP1B crystal. The structure of the intermediate at 2.5-A resolution reveals that a conformationally flexible loop (the WPD loop) is closed over the entrance to the catalytic site, sequestering the phosphocysteine intermediate and catalytic site water molecules and preventing nonspecific phosphoryltransfer reactions to extraneous phosphoryl acceptors. One of the catalytic site water molecules, the likely nucleophile, forms a hydrogen bond to the putative catalytic base, Asp-181. In the wild-type enzyme, the nucleophilic water molecule would be coordinated by the side chain of Gln-262. In combination with our previous structural data, we can now visualize each of the reaction steps of the PTP catalytic pathway. The hydrolysis of the cysteinyl-phosphate intermediate of PTPs is reminiscent of GTP hydrolysis by the GTPases, in that both families of enzymes utilize an invariant Gln residue to coordinate the attacking nucleophilic water molecule.

PubMed: 9553104
DOI: 10.1074/jbc.273.17.10454

実験手法

X-RAY DIFFRACTION (2.5 Å)