2oz5: Difference between revisions

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[[Image:2oz5.png|left|200px]]
==Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS==
<StructureSection load='2oz5' size='340' side='right' caption='[[2oz5]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2oz5]] is a 2 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OZ5 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7XY:{(3-CHLOROBENZYL)[(5-{[(3,3-DIPHENYLPROPYL)AMINO]SULFONYL}-2-THIENYL)METHYL]AMINO}(OXO)ACETIC+ACID'>7XY</scene><br>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ptpB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oz5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2oz5 RCSB], [http://www.ebi.ac.uk/pdbsum/2oz5 PDBsum]</span></td></tr>
<table>
== 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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


{{STRUCTURE_2oz5|  PDB=2oz5  |  SCENE=  }}
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:17437721<ref>PMID:17437721</ref>


===Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_17437721}}
 
==About this Structure==
[[2oz5]] is a 2 chain structure with 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].


==See Also==
==See Also==
*[[Tyrosine phosphatase|Tyrosine phosphatase]]
*[[Tyrosine phosphatase|Tyrosine phosphatase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:017437721</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Alber, T.]]
[[Category: Alber, T.]]
Retrieved from "https://proteopedia.org/2oz5"