1R6H

Solution Structure of human PRL-3

1R6H の概要

• エントリーDOI: 10.2210/pdb1r6h/pdb
• 分子名称: protein tyrosine phosphatase type IVA, member 3 isoform 1 (1 entity in total)
• 機能のキーワード: dual specificity phosphatase fold, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane: O75365
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19412.56

構造登録者

Kozlov, G.,Gehring, K.,Ekiel, I. (登録日: 2003-10-15, 公開日: 2004-01-13, 最終更新日: 2024-05-22)

主引用文献

Kozlov, G.,Cheng, J.,Ziomek, E.,Banville, D.,Gehring, K.,Ekiel, I.
Structural Insights into Molecular Function of the Metastasis-associated Phosphatase PRL-3.
J.Biol.Chem., 279:11882-11889, 2004

PubMed Abstract: Phosphatases and kinases are the cellular signal transduction enzymes that control protein phosphorylation. PRL phosphatases constitute a novel class of small (20 kDa), prenylated phosphatases with oncogenic activity. In particular, PRL-3 is consistently overexpressed in liver metastasis in colorectal cancer cells and represents a new therapeutic target. Here, we present the solution structure of PRL-3, the first structure of a PRL phosphatase. The structure places PRL phosphatases in the class of dual specificity phosphatases with closest structural homology to the VHR phosphatase. The structure, coupled with kinetic studies of site-directed mutants, identifies functionally important residues and reveals unique features, differentiating PRLs from other phosphatases. These differences include an unusually hydrophobic active site without the catalytically important serine/threonine found in most other phosphatases. The position of the general acid loop indicates the presence of conformational change upon catalysis. The studies also identify a potential regulatory role of Cys(49) that forms an intramolecular disulfide bond with the catalytic Cys(104) even under mildly reducing conditions. Molecular modeling of the highly homologous PRL-1 and PRL-2 phosphatases revealed unique surface elements that are potentially important for specificity.

PubMed: 14704153
DOI: 10.1074/jbc.M312905200

実験手法

SOLUTION NMR