6ow7

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'''Unreleased structure'''
 
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The entry 6ow7 is ON HOLD until Paper Publication
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==X-ray Structure of Polypeptide Deformylase with a Piperazic Acid==
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<StructureSection load='6ow7' size='340' side='right'caption='[[6ow7]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6ow7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OW7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OW7 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N9Y:(3S)-2-{(2R)-2-(cyclopentylmethyl)-3-[formyl(hydroxy)amino]propanoyl}-N-(pyridin-2-yl)hexahydropyridazine-3-carboxamide'>N9Y</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide_deformylase Peptide deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.88 3.5.1.88] </span></td></tr>
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<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=6ow7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ow7 OCA], [http://pdbe.org/6ow7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ow7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ow7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ow7 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/Q939R9_STREE Q939R9_STREE]] Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions (By similarity).[HAMAP-Rule:MF_00163]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The discovery of a novel series of peptide deformylase inhibitors incorporating a piperazic acid amino acid found in nature is described. These compounds demonstrated potent in vitro enzymatic potency and antimicrobial activity. Crystal structure analysis revealed the piperazic acid optimized a key contact with the PDF protein that accounted for the increased enzymatic potency of these compounds. We describe lead optimization of the P3' region of the series that resulted in a compound with good potency against three target organisms. One molecule showed in vivo efficacy in a rat respiratory infection model but ultimately did not meet candidate progression criteria.
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Authors: Campobasso, N., Spletstoser, J., Ward, P.
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Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections.,Spletstoser JT, Dreabit J, Knox AN, Benowitz A, Campobasso N, Ward P, Cui G, Lewandowski T, McCloskey L, Aubart KM Bioorg Med Chem Lett. 2019 May 16. pii: S0960-894X(19)30325-7. doi:, 10.1016/j.bmcl.2019.05.028. PMID:31160176<ref>PMID:31160176</ref>
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Description: X-ray Structure of Polypeptide Deformylase with a Piperazic Acid
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Ward, P]]
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<div class="pdbe-citations 6ow7" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Peptide deformylase]]
[[Category: Campobasso, N]]
[[Category: Campobasso, N]]
[[Category: Spletstoser, J]]
[[Category: Spletstoser, J]]
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[[Category: Ward, P]]
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[[Category: Complex]]
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[[Category: Enzyme]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Inhibitor]]
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[[Category: Metal protein]]

Revision as of 07:01, 26 June 2019

X-ray Structure of Polypeptide Deformylase with a Piperazic Acid

PDB ID 6ow7

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