2y2f: Difference between revisions
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New page: '''Unreleased structure''' The entry 2y2f is ON HOLD Authors: Lountos, G.T., Bahta, M., Dyas, B., Ulrich, R.G., Waugh, D.S., Burke, T.R. Description: Crystal structure of Yersinia pest... |
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==Crystal structure of Yersinia pestis YopH in complex with an aminooxy- containing platform compound for inhibitor design== | |||
<StructureSection load='2y2f' size='340' side='right'caption='[[2y2f]], [[Resolution|resolution]] 1.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2y2f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y2F 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]] 1.78Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=YI1:[4-[3-(DIFLUORO-PHOSPHONO-METHYL)PHENYL]PHENYL]METHOXYAZANIUM'>YI1</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=2y2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y2f OCA], [https://pdbe.org/2y2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y2f RCSB], [https://www.ebi.ac.uk/pdbsum/2y2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y2f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O68720_YERPE O68720_YERPE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Our current study reports the first K(M) optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K(M) = 80 muM) was converted from a substrate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid and by attachment of an aminooxy handle for further structural optimization by oxime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequently employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC(50) = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition of intracellular Y. pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH. | |||
Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase.,Bahta M, Lountos GT, Dyas B, Kim SE, Ulrich RG, Waugh DS, Burke TR Jr J Med Chem. 2011 Apr 28;54(8):2933-43. Epub 2011 Mar 28. PMID:21443195<ref>PMID:21443195</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2y2f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Yersinia pestis]] | |||
[[Category: Bahta M]] | |||
[[Category: Burke TR]] | |||
[[Category: Dyas B]] | |||
[[Category: Lountos GT]] | |||
[[Category: Ulrich RG]] | |||
[[Category: Waugh DS]] | |||
Latest revision as of 10:43, 20 December 2023
Crystal structure of Yersinia pestis YopH in complex with an aminooxy- containing platform compound for inhibitor design
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