5k25: Difference between revisions
New page: '''Unreleased structure''' The entry 5k25 is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Crystal structure of human phosphatase PRL-2 in complex with the ADP-bound Bateman domain of human magnesium transporter CNNM3== | ||
<StructureSection load='5k25' size='340' side='right'caption='[[5k25]], [[Resolution|resolution]] 3.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5k25]] 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=5K25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K25 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.05Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></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=5k25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k25 OCA], [https://pdbe.org/5k25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k25 RCSB], [https://www.ebi.ac.uk/pdbsum/5k25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k25 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:28246390</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5k25" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]] | |||
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gehring K]] | |||
[[Category: Gulerez I]] | |||
[[Category: Kozlov G]] | |||
Latest revision as of 22:18, 20 September 2023
Crystal structure of human phosphatase PRL-2 in complex with the ADP-bound Bateman domain of human magnesium transporter CNNM3Crystal structure of human phosphatase PRL-2 in complex with the ADP-bound Bateman domain of human magnesium transporter CNNM3
Structural highlights
FunctionTP4A2_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 PubMedThe 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 AlsoReferences
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