1r6h
From Proteopedia
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[[Image:1r6h.gif|left|200px]] | [[Image:1r6h.gif|left|200px]] | ||
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'''Solution Structure of human PRL-3''' | '''Solution Structure of human PRL-3''' | ||
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[[Category: Gehring, K.]] | [[Category: Gehring, K.]] | ||
[[Category: Kozlov, G.]] | [[Category: Kozlov, G.]] | ||
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Revision as of 04:08, 3 May 2008
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. 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 Sat May 3 07:08:33 2008