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| | <StructureSection load='5hk9' size='340' side='right'caption='[[5hk9]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5hk9' size='340' side='right'caption='[[5hk9]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hk9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseab Pseab]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HK9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HK9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hk9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_UCBPP-PA14 Pseudomonas aeruginosa UCBPP-PA14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HK9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=64O:N-(4-{[4-(CARBAMOYLAMINO)-6-HYDROXYBIPHENYL-3-YL]OXY}-3,5-DICHLOROPHENYL)PROPANAMIDE'>64O</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kd2|3kd2]], [[4yx9|4yx9]], [[5hkb|5hkb]], [[5hka|5hka]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=64O:N-(4-{[4-(CARBAMOYLAMINO)-6-HYDROXYBIPHENYL-3-YL]OXY}-3,5-DICHLOROPHENYL)PROPANAMIDE'>64O</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PA14_26090 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208963 PSEAB])</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=5hk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hk9 OCA], [https://pdbe.org/5hk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hk9 RCSB], [https://www.ebi.ac.uk/pdbsum/5hk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hk9 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hk9 OCA], [http://pdbe.org/5hk9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hk9 RCSB], [http://www.ebi.ac.uk/pdbsum/5hk9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hk9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H2ZD27_PSEAB A0A0H2ZD27_PSEAB] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pseab]] | + | [[Category: Pseudomonas aeruginosa UCBPP-PA14]] |
| - | [[Category: Hvorecny, K L]] | + | [[Category: Hvorecny KL]] |
| - | [[Category: Madden, D R]] | + | [[Category: Madden DR]] |
| - | [[Category: Bacterial epoxide hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
A0A0H2ZD27_PSEAB
Publication Abstract from PubMed
The virulence factor cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is secreted by Pseudomonas aeruginosa and is the founding member of a distinct class of epoxide hydrolases (EHs) that triggers the catalysis-dependent degradation of the CFTR. We describe here the development of a series of potent and selective Cif inhibitors by structure-based drug design. Initial screening revealed 1a (KB2115), a thyroid hormone analog, as a lead compound with low micromolar potency. Structural requirements for potency were systematically probed, and interactions between Cif and 1a were characterized by X-ray crystallography. On the basis of these data, new compounds were designed to yield additional hydrogen bonding with residues of the Cif active site. From this effort, three compounds were identified that are 10-fold more potent toward Cif than our first-generation inhibitors and have no detectable thyroid hormone-like activity. These inhibitors will be useful tools to study the pathological role of Cif and have the potential for clinical application.
Rational Design of Potent and Selective Inhibitors of an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa.,Kitamura S, Hvorecny KL, Niu J, Hammock BD, Madden DR, Morisseau C J Med Chem. 2016 May 26;59(10):4790-9. doi: 10.1021/acs.jmedchem.6b00173. Epub, 2016 May 4. PMID:27120257[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kitamura S, Hvorecny KL, Niu J, Hammock BD, Madden DR, Morisseau C. Rational Design of Potent and Selective Inhibitors of an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa. J Med Chem. 2016 May 26;59(10):4790-9. doi: 10.1021/acs.jmedchem.6b00173. Epub, 2016 May 4. PMID:27120257 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00173
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