1r6h

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[[Image:1r6h.gif|left|200px]]
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{{Structure
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|PDB= 1r6h |SIZE=350|CAPTION= <scene name='initialview01'>1r6h</scene>
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The line below this paragraph, containing "STRUCTURE_1r6h", creates the "Structure Box" on the page.
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1r6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6h OCA], [http://www.ebi.ac.uk/pdbsum/1r6h PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1r6h RCSB]</span>
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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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[[Category: dual specificity phosphatase fold]]
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[[Category: Dual specificity phosphatase fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:08:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:23:54 2008''
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Revision as of 04:08, 3 May 2008

Template:STRUCTURE 1r6h

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

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