4u3d
From Proteopedia
(Difference between revisions)
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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=4u3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u3d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u3d RCSB], [http://www.ebi.ac.uk/pdbsum/4u3d 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=4u3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u3d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u3d RCSB], [http://www.ebi.ac.uk/pdbsum/4u3d PDBsum]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In the search for novel Gram-negative agents, we performed a comprehensive search of the AstraZeneca collection and identified a tetrahydropyran-based matrix metalloprotease (MMP) inhibitor that demonstrated nanomolar inhibition of UDP-3-O-(acyl)-N-acetylglucosamine deacetylase (LpxC). Crystallographic studies in Aquifex aeolicus LpxC indicated the tetrahydropyran engaged in the same hydrogen bonds and van der Waals interactions as other known inhibitors. Systematic optimization of three locales on the scaffold provided compounds with improved Gram-negative activity. However, the optimization of LpxC activity was not accompanied by reduced inhibition of MMPs. Comparison of the crystal structure of the native product, UDP-3-O-(acyl)-glucosamine, in Aquifex aeolicus to the structure of a tetrahydropyran-based inhibitor indicates pathways for future optimization. | ||
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| + | Synthesis, Structure, and SAR of Tetrahydropyran-Based LpxC Inhibitors.,Murphy-Benenato KE, Olivier N, Choy A, Ross PL, Miller MD, Thresher J, Gao N, Hale MR ACS Med Chem Lett. 2014 Sep 23;5(11):1213-1218. eCollection 2014 Nov 13. PMID:25408833<ref>PMID:25408833</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Olivier, N B | + | [[Category: Olivier, N B]] |
[[Category: Antibacterial]] | [[Category: Antibacterial]] | ||
[[Category: Gram negative bacteria]] | [[Category: Gram negative bacteria]] | ||
Revision as of 12:20, 10 December 2014
LpxC from A.Aaeolicus in complex with 4-[[4-[2-[4-(morpholinomethyl)phenyl]ethynyl]phenoxy]methyl]tetrahydropyran-4-carbohydroxamic acid (compound 9)
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