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| | ==Crystal structure of the complex between human phosphatase PRL-2 in the oxidized state with the Bateman domain of human magnesium transporter CNNM3== | | ==Crystal structure of the complex between human phosphatase PRL-2 in the oxidized state with the Bateman domain of human magnesium transporter CNNM3== |
| - | <StructureSection load='5k23' size='340' side='right' caption='[[5k23]], [[Resolution|resolution]] 2.96Å' scene=''> | + | <StructureSection load='5k23' size='340' side='right'caption='[[5k23]], [[Resolution|resolution]] 2.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k23]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K23 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K23 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k23]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K23 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k22|5k22]], [[5k24|5k24]], [[5k25|5k25]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.96Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTP4A2, PRL2, PTPCAAX2, BM-008 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CNNM3, ACDP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5k23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k23 OCA], [https://pdbe.org/5k23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k23 RCSB], [https://www.ebi.ac.uk/pdbsum/5k23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k23 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k23 OCA], [http://pdbe.org/5k23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k23 RCSB], [http://www.ebi.ac.uk/pdbsum/5k23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k23 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TP4A2_HUMAN TP4A2_HUMAN]] Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.<ref>PMID:14643450</ref> [[http://www.uniprot.org/uniprot/CNNM3_HUMAN CNNM3_HUMAN]] Probable metal transporter. | + | [https://www.uniprot.org/uniprot/TP4A2_HUMAN TP4A2_HUMAN] Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.<ref>PMID:14643450</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | + | *[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]] |
| | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Gehring, K]] | + | [[Category: Gehring K]] |
| - | [[Category: Gulerez, I]] | + | [[Category: Gulerez I]] |
| - | [[Category: Kozlov, G]] | + | [[Category: Kozlov G]] |
| - | [[Category: Complex]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-transporter protein-protein binding complex]]
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| - | [[Category: Magnesium transporter]]
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| - | [[Category: Phosphatase]]
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| - | [[Category: Protein binding]]
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| Structural highlights
Function
TP4A2_HUMAN Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.[1]
Publication Abstract from PubMed
The phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation. We use comprehensive mutagenesis of the PRL3 catalytic site to quantify the importance of different PRL amino acids, including cysteine 104, leucine 108, and arginine 110, for CNNM binding and phosphatase activity. We show the PRL3 R138E mutant is selectively deficient in CNNM3 binding with the potential to distinguish between the downstream effects of phosphatase and CNNM-binding activities in vivo. Through a novel activity assay, we show that PRL3 has magnesium-sensitive phosphatase activity with ATP and other nucleotides. Our results identify a strong correlation between phosphatase activity and CNNM binding and support the contention that PRL function as pseudophosphatases regulated by chemical modifications of their catalytic cysteine.
PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3.,Zhang H, Kozlov G, Li X, Wu H, Gulerez I, Gehring K Sci Rep. 2017 Mar 3;7(1):48. doi: 10.1038/s41598-017-00147-2. PMID:28246390[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Werner SR, Lee PA, DeCamp MW, Crowell DN, Randall SK, Crowell PL. Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases. Cancer Lett. 2003 Dec 30;202(2):201-11. PMID:14643450
- ↑ Zhang H, Kozlov G, Li X, Wu H, Gulerez I, Gehring K. PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3. Sci Rep. 2017 Mar 3;7(1):48. doi: 10.1038/s41598-017-00147-2. PMID:28246390 doi:http://dx.doi.org/10.1038/s41598-017-00147-2
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