5dro: Difference between revisions
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==Structure of the Aquifex aeolicus LpxC/LPC-011 Complex== | |||
<StructureSection load='5dro' size='340' side='right' caption='[[5dro]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dro]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DRO FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZH2:4-[4-(4-AMINOPHENYL)BUTA-1,3-DIYN-1-YL]-N-[(2S,3R)-3-HYDROXY-1-(HYDROXYAMINO)-1-OXOBUTAN-2-YL]BENZAMIDE'>ZH2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5drp|5drp]], [[5drq|5drq]], [[5drr|5drr]]</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=5dro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dro OCA], [http://pdbe.org/5dro PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dro RCSB], [http://www.ebi.ac.uk/pdbsum/5dro PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/LPXC_AQUAE LPXC_AQUAE]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC-an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target-access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics. | |||
Drug design from the cryptic inhibitor envelope.,Lee CJ, Liang X, Wu Q, Najeeb J, Zhao J, Gopalaswamy R, Titecat M, Sebbane F, Lemaitre N, Toone EJ, Zhou P Nat Commun. 2016 Feb 25;7:10638. doi: 10.1038/ncomms10638. PMID:26912110<ref>PMID:26912110</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5dro" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lee, C J]] | |||
[[Category: Najeeb, J]] | [[Category: Najeeb, J]] | ||
[[Category: Zhou, P]] | [[Category: Zhou, P]] | ||
[[Category: Gram-negative bacteria]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Inhibitor]] | |||
[[Category: Lipid some]] | |||
[[Category: Lpxc]] | |||