2jt2: Difference between revisions
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{{ | ==Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex== | ||
<StructureSection load='2jt2' size='340' side='right' caption='[[2jt2]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''> | |||
=== | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jt2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JT2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JT2 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C90:N-{(1S,2R)-2-HYDROXY-1-[(HYDROXYAMINO)CARBONYL]PROPYL}-4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}BENZAMIDE'>C90</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpxC, envA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 Aquifex aeolicus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jt2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jt2 RCSB], [http://www.ebi.ac.uk/pdbsum/2jt2 PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jt/2jt2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC-CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage. | |||
Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding.,Barb AW, Jiang L, Raetz CR, Zhou P Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. PMID:18025458<ref>PMID:18025458</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
==See Also== | |||
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: Barb, A W.]] | [[Category: Barb, A W.]] | ||
Revision as of 09:04, 30 September 2014
Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex
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