1r6h
From Proteopedia
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Solution Structure of human PRL-3
Overview
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.
About this Structure
1R6H is a Single protein structure of sequence from Homo sapiens. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Structural insights into molecular function of the metastasis-associated phosphatase PRL-3., Kozlov G, Cheng J, Ziomek E, Banville D, Gehring K, Ekiel I, J Biol Chem. 2004 Mar 19;279(12):11882-9. Epub 2004 Jan 1. PMID:14704153
Page seeded by OCA on Mon Nov 12 19:00:37 2007
