2y2f: Difference between revisions

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-[[Image:2y2f.png|left|200px]]
-{{STRUCTURE_2y2f|  PDB=2y2f  |  SCENE=  }}
+==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]] 1.78&Aring;' 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]] 1.78&#8491;</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.
-===CRYSTAL STRUCTURE OF YERSINIA PESTIS YOPH IN COMPLEX WITH AN AMINOOXY-CONTAINING PLATFORM COMPOUND FOR INHIBITOR DESIGN===
+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>
-{{ABSTRACT_PUBMED_21443195}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2y2f" style="background-color:#fffaf0;"></div>
-[[2y2f]] is a 1 chain structure of [[Proten tyrosine phosphatase]] and [[Tyrosine phosphatase]] with sequence from [http://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].
 ==See Also==
-*[[Proten tyrosine phosphatase|Proten tyrosine phosphatase]]
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
-*[[Tyrosine phosphatase|Tyrosine phosphatase]]
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:021443195</ref><references group="xtra"/>
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Yersinia pestis]]
-[[Category: Bahta, M.]]
+[[Category: Bahta M]]
-[[Category: Burke, T R.]]
+[[Category: Burke TR]]
-[[Category: Dyas, B.]]
+[[Category: Dyas B]]
-[[Category: Lountos, G T.]]
+[[Category: Lountos GT]]
-[[Category: Ulrich, R G.]]
+[[Category: Ulrich RG]]
-[[Category: Waugh, D S.]]
+[[Category: Waugh DS]]
-[[Category: Hydrolase]]
-[[Category: Protein tyrosine phosphatase]]