2oz5: Difference between revisions

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-[[Image:2oz5.gif|left|200px]]
- {{Structure
+==Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS==
-|PDB= 2oz5 |SIZE=350|CAPTION= <scene name='initialview01'>2oz5</scene>, resolution 2.000&Aring;
+<StructureSection load='2oz5' size='340' side='right'caption='[[2oz5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=7XY:{(3-CHLOROBENZYL)[(5-{[(3,3-DIPHENYLPROPYL)AMINO]SULFONYL}-2-THIENYL)METHYL]AMINO}(OXO)ACETIC ACID'>7XY</scene>
+<table><tr><td colspan='2'>[[2oz5]] is a 2 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=2OZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OZ5 FirstGlance]. <br>
-|ACTIVITY=
+</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&#8491;</td></tr>
-|GENE= ptpB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7XY:{(3-CHLOROBENZYL)[(5-{[(3,3-DIPHENYLPROPYL)AMINO]SULFONYL}-2-THIENYL)METHYL]AMINO}(OXO)ACETIC+ACID'>7XY</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=2oz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oz5 OCA], [https://pdbe.org/2oz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oz5 RCSB], [https://www.ebi.ac.uk/pdbsum/2oz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oz5 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/P96830_MYCTO P96830_MYCTO]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oz/2oz5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </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/main_output.php?pdb_ID=2oz5 ConSurf].
+<div style="clear:both"></div>
-'''Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS'''
+==See Also==
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
+__TOC__
-==Overview==
+</StructureSection>
-Tyrosine kinases and phosphatases establish the crucial balance of tyrosine phosphorylation in cellular signaling, but creating specific inhibitors of protein Tyr phosphatases (PTPs) remains a challenge. Here, we report the development of a potent, selective inhibitor of Mycobacterium tuberculosis PtpB, a bacterial PTP that is secreted into host cells where it disrupts unidentified signaling pathways. The inhibitor, (oxalylamino-methylene)-thiophene sulfonamide (OMTS), showed an IC(50) of 440 +/- 50 nM and &gt;60-fold specificity for PtpB over six human PTPs. The 2 A resolution crystal structure of PtpB in complex with OMTS revealed a large rearrangement of the enzyme, with some residues shifting &gt;27 A relative to the PtpB:PO(4) complex. Extensive contacts with the catalytic loop provide a potential basis for inhibitor selectivity. Two OMTS molecules bound adjacent to each other, raising the possibility of a second substrate phosphotyrosine binding site in PtpB. The PtpB:OMTS structure provides an unanticipated framework to guide inhibitor improvement.
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-==About this Structure==
+[[Category: Alber T]]
-OZ5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OZ5 OCA].
+[[Category: Gee CL]]
+[[Category: Grundner C]]
-==Reference==
-Structural basis for selective inhibition of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB., Grundner C, Perrin D, Hooft van Huijsduijnen R, Swinnen D, Gonzalez J, Gee CL, Wells TN, Alber T, Structure. 2007 Apr;15(4):499-509. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17437721 17437721]
-[[Category: Mycobacterium tuberculosis]]
-[[Category: Single protein]]
-[[Category: Alber, T.]]
-[[Category: Gee, C L.]]
-[[Category: Grundner, C.]]
-[[Category: TBSGC, TB Structural Genomics Consortium.]]
-[[Category: 7XY]]
-[[Category: protein tyrosine phosphatase in complex with small molecule inhibitor]]
-[[Category: structural genomic]]
-[[Category: tb structural genomics consortium]]
-[[Category: tbsgc]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:06:28 2008''