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| - | ==CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF SERINE THREONINE PROTEIN PHOSPHATASE PSTP IN COMPLEX WITH 2 MANGANESE IONS.== | + | |
| - | <StructureSection load='2cm1' size='340' side='right' caption='[[2cm1]], [[Resolution|resolution]] 2.00Å' scene=''> | + | ==Crystal structure of the catalytic domain of serine threonine protein phosphatase PstP in complex with 2 Manganese ions.== |
| | + | <StructureSection load='2cm1' size='340' side='right'caption='[[2cm1]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cm1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CM1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CM1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cm1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CM1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1txo|1txo]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></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=2cm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm1 OCA], [https://pdbe.org/2cm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cm1 RCSB], [https://www.ebi.ac.uk/pdbsum/2cm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cm1 ProSAT]</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=2cm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm1 OCA], [http://pdbe.org/2cm1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cm1 RCSB], [http://www.ebi.ac.uk/pdbsum/2cm1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PSTP_MYCTU PSTP_MYCTU] The only predicted protein phosphatase in M.tuberculosis, it dephosphorylates at least 5 protein kinases (PknA, PknB, PknD, PknE and PknF) and the penicillin-binding protein PBPA.<ref>PMID:14575702</ref> <ref>PMID:12950916</ref> <ref>PMID:15967413</ref> <ref>PMID:16436437</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cm/2cm1_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cm/2cm1_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cm1 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]] | + | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Alzari, P M]] | + | [[Category: Alzari PM]] |
| - | [[Category: Bellinzoni, M]] | + | [[Category: Bellinzoni M]] |
| - | [[Category: Villarino, A]] | + | [[Category: Villarino A]] |
| - | [[Category: Wehenkel, A]] | + | [[Category: Wehenkel A]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase hypothetical protein]]
| + | |
| - | [[Category: Mycobacterium tuberculosis]]
| + | |
| - | [[Category: Ser/thr protein phosphatase pstp]]
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| Structural highlights
Function
PSTP_MYCTU The only predicted protein phosphatase in M.tuberculosis, it dephosphorylates at least 5 protein kinases (PknA, PknB, PknD, PknE and PknF) and the penicillin-binding protein PBPA.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Phospho-Ser/Thr protein phosphatases (PPs) are dinuclear metalloenzymes classed into two large families, PPP and PPM, on the basis of sequence similarity and metal ion dependence. The archetype of the PPM family is the alpha isoform of human PP2C (PP2Calpha), which folds into an alpha/beta domain similar to those of PPP enzymes. The recent structural studies of three bacterial PPM phosphatases, Mycobacterium tuberculosis MtPstP, Mycobacterium smegmatis MspP, and Streptococcus agalactiae STP, confirmed the conservation of the overall fold and dinuclear metal center in the family, but surprisingly revealed the presence of a third conserved metal-binding site in the active site. To gain insight into the roles of the three-metal center in bacterial enzymes, we report structural and metal-binding studies of MtPstP and MspP. The structure of MtPstP in a new trigonal crystal form revealed a fully active enzyme with the canonical dinuclear metal center but without the third metal ion bound to the catalytic site. The absence of metal correlates with a partially unstructured flap segment, indicating that the third manganese ion contributes to reposition the flap, but is dispensable for catalysis. Studies of metal binding to MspP using isothermal titration calorimetry revealed that the three Mn(2+)-binding sites display distinct affinities, with dissociation constants in the nano- and micromolar range for the two catalytic metal ions and a significantly lower affinity for the third metal-binding site. In agreement, the structure of inactive MspP at acidic pH was determined at atomic resolution and shown to lack the third metal ion in the active site. Structural comparisons of all bacterial phosphatases revealed positional variations in the third metal-binding site that are correlated with the presence of bound substrate and the conformation of the flap segment, supporting a role of this metal ion in assisting enzyme-substrate interactions.
Structural and binding studies of the three-metal center in two mycobacterial PPM Ser/Thr protein phosphatases.,Wehenkel A, Bellinzoni M, Schaeffer F, Villarino A, Alzari PM J Mol Biol. 2007 Dec 7;374(4):890-8. Epub 2007 Oct 2. PMID:17961594[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chopra P, Singh B, Singh R, Vohra R, Koul A, Meena LS, Koduri H, Ghildiyal M, Deol P, Das TK, Tyagi AK, Singh Y. Phosphoprotein phosphatase of Mycobacterium tuberculosis dephosphorylates serine-threonine kinases PknA and PknB. Biochem Biophys Res Commun. 2003 Nov 7;311(1):112-20. PMID:14575702
- ↑ Boitel B, Ortiz-Lombardia M, Duran R, Pompeo F, Cole ST, Cervenansky C, Alzari PM. PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in Mycobacterium tuberculosis. Mol Microbiol. 2003 Sep;49(6):1493-508. PMID:12950916
- ↑ Duran R, Villarino A, Bellinzoni M, Wehenkel A, Fernandez P, Boitel B, Cole ST, Alzari PM, Cervenansky C. Conserved autophosphorylation pattern in activation loops and juxtamembrane regions of Mycobacterium tuberculosis Ser/Thr protein kinases. Biochem Biophys Res Commun. 2005 Aug 5;333(3):858-67. PMID:15967413 doi:http://dx.doi.org/S0006-291X(05)01184-8
- ↑ Dasgupta A, Datta P, Kundu M, Basu J. The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division. Microbiology. 2006 Feb;152(Pt 2):493-504. PMID:16436437 doi:http://dx.doi.org/152/2/493
- ↑ Wehenkel A, Bellinzoni M, Schaeffer F, Villarino A, Alzari PM. Structural and binding studies of the three-metal center in two mycobacterial PPM Ser/Thr protein phosphatases. J Mol Biol. 2007 Dec 7;374(4):890-8. Epub 2007 Oct 2. PMID:17961594 doi:http://dx.doi.org/10.1016/j.jmb.2007.09.076
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