2oz5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
<StructureSection load='2oz5' size='340' side='right' caption='[[2oz5]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2oz5' size='340' side='right' caption='[[2oz5]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2oz5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2oz5]] is a 2 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=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 id='ligand'><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></td></tr> | </td></tr><tr id='ligand'><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></td></tr> | ||
<tr id='gene'><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= | <tr id='gene'><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=83332 MYCTU])</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=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> | <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=2oz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oz5 OCA], [http://pdbe.org/2oz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2oz5 RCSB], [http://www.ebi.ac.uk/pdbsum/2oz5 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 25: | Line 25: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2oz5" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 32: | Line 33: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Myctu]] | ||
[[Category: Alber, T]] | [[Category: Alber, T]] | ||
[[Category: Gee, C L]] | [[Category: Gee, C L]] | ||
Revision as of 03:30, 12 September 2015
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
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 PubMedTyrosine 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 >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 >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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||