1R6H
Solution Structure of human PRL-3
Summary for 1R6H
| Entry DOI | 10.2210/pdb1r6h/pdb |
| Descriptor | protein tyrosine phosphatase type IVA, member 3 isoform 1 (1 entity in total) |
| Functional Keywords | dual specificity phosphatase fold, hydrolase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane: O75365 |
| Total number of polymer chains | 1 |
| Total formula weight | 19412.56 |
| Authors | Kozlov, G.,Gehring, K.,Ekiel, I. (deposition date: 2003-10-15, release date: 2004-01-13, Last modification date: 2024-05-22) |
| Primary citation | 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 Cited by 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: 14704153DOI: 10.1074/jbc.M312905200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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