|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structures of YopH complexed with PVSN and PVS, inhibitors of YopH which co-valent bind to Cys of active site== | | ==Crystal structures of YopH complexed with PVSN and PVS, inhibitors of YopH which co-valent bind to Cys of active site== |
| - | <StructureSection load='3blt' size='340' side='right' caption='[[3blt]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='3blt' size='340' side='right'caption='[[3blt]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3blt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_enterocoliticum"_schleifstein_and_coleman_1939 "bacterium enterocoliticum" schleifstein and coleman 1939]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BLT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BLT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3blt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Yersinia_enterocolitica Yersinia enterocolitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BLT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BLT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PSY:PHENYL+ETHENESULFONATE'>PSY</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3blu|3blu]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PSY:PHENYL+ETHENESULFONATE'>PSY</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">yopH, yop51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=630 "Bacterium enterocoliticum" Schleifstein and Coleman 1939])</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=3blt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blt OCA], [https://pdbe.org/3blt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3blt RCSB], [https://www.ebi.ac.uk/pdbsum/3blt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3blt 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=3blt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3blt OCA], [http://pdbe.org/3blt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3blt RCSB], [http://www.ebi.ac.uk/pdbsum/3blt PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/YOPH_YEREN YOPH_YEREN]] Essential virulence determinant. This protein is a protein tyrosine phosphatase. The essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation. It contributes to the ability of the bacteria to resist phagocytosis by peritoneal macrophages. | + | [https://www.uniprot.org/uniprot/YOPH_YEREN YOPH_YEREN] Essential virulence determinant. This protein is a protein tyrosine phosphatase. The essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation. It contributes to the ability of the bacteria to resist phagocytosis by peritoneal macrophages. |
| | == 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/bl/3blt_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3blt_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 30: |
Line 29: |
| | </div> | | </div> |
| | <div class="pdbe-citations 3blt" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3blt" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacterium enterocoliticum schleifstein and coleman 1939]] | + | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Yersinia enterocolitica]] |
| - | [[Category: Liu, S]] | + | [[Category: Liu S]] |
| - | [[Category: Zhang, Z-Y]] | + | [[Category: Zhang Z-Y]] |
| - | [[Category: Binding affinity]]
| + | |
| - | [[Category: Binding selectivity]]
| + | |
| - | [[Category: Co-valent binding]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Outer membrane]]
| + | |
| - | [[Category: Protein phosphatase]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Virulence]]
| + | |
| Structural highlights
Function
YOPH_YEREN Essential virulence determinant. This protein is a protein tyrosine phosphatase. The essential function of YopH in Yersinia pathogenesis is host-protein dephosphorylation. It contributes to the ability of the bacteria to resist phagocytosis by peritoneal macrophages.
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
Protein tyrosine phosphatases (PTPs) play key roles in the regulation of normal and pathological processes ranging from cell proliferation, differentiation, metabolism, and survival to many human diseases including cancer and diabetes. Functional studies of PTP can be greatly facilitated by small molecule probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. In this article, we characterize phenyl vinyl sulfonate (PVSN) and phenyl vinyl sulfone (PVS) as a new class of mechanism-based PTP probes. PVSN and PVS inactivate a broad range of PTPs in a time- and concentration-dependent fashion. The PVSN- and PVS-mediated PTP inactivation is active site-directed and irreversible, resulting from a Michael addition of the active-site Cys Sgamma onto the terminal carbon of the vinyl group. Structural and mechanistic analyses reveal the molecular basis for the preference of PVSN/PVS toward the PTPs, which lies in the ability of PVSN and PVS to engage the conserved structural and catalytic machinery of the PTP active site. In contrast to early alpha-bromobenzyl phosphonate-based probes, PVSN and PVS are resistant to solvolysis and are cell-permeable and thus hold promise for in vivo applications. Collectively, these properties bode well for the development of aryl vinyl sulfonate/sulfone-based PTP probes to interrogate PTP activity in complex proteomes.
Aryl Vinyl Sulfonates and Sulfones as Active Site-Directed and Mechanism-Based Probes for Protein Tyrosine Phosphatases.,Liu S, Zhou B, Yang H, He Y, Jiang ZX, Kumar S, Wu L, Zhang ZY J Am Chem Soc. 2008 Jun 4;. PMID:18528979[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu S, Zhou B, Yang H, He Y, Jiang ZX, Kumar S, Wu L, Zhang ZY. Aryl Vinyl Sulfonates and Sulfones as Active Site-Directed and Mechanism-Based Probes for Protein Tyrosine Phosphatases. J Am Chem Soc. 2008 Jun 4;. PMID:18528979 doi:10.1021/ja711125p
|
