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[[Image:2oz5.gif|left|200px]]<br /><applet load="2oz5" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2oz5, resolution 2.000&Aring;" />
'''Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS'''<br />


==Overview==
==Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS==
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.
<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 [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>
</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>
<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>


==About this Structure==
==See Also==
2OZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=7XY:'>7XY</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OZ5 OCA].
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17437721 17437721]
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Single protein]]
[[Category: Alber T]]
[[Category: Alber, T.]]
[[Category: Gee CL]]
[[Category: Gee, C L.]]
[[Category: Grundner C]]
[[Category: Grundner, C.]]
[[Category: TBSGC, TB Structural Genomics Consortium.]]
[[Category: 7XY]]
[[Category: protein tyrosine phosphatase in complex with small molecule inhibitor]]
[[Category: structural genomics]]
[[Category: tb structural genomics consortium]]
[[Category: tbsgc]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:24:16 2008''

Latest revision as of 12:06, 21 February 2024

Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTSCrystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS

Structural highlights

2oz5 is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P96830_MYCTO

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2oz5, resolution 2.00Å

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