2j7l: Difference between revisions
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[[Image: | ==E.COLI P PILUS CHAPERONE PAPD IN COMPLEX WITH A PILUS BIOGENESIS INHIBITOR, PILICIDE 2C== | ||
<StructureSection load='2j7l' size='340' side='right' caption='[[2j7l]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2j7l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J7L FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XC2:(3R)-8-CYCLOPROPYL-6-(MORPHOLIN-4-YLMETHYL)-7-(1-NAPHTHYLMETHYL)-5-OXO-2,3-DIHYDRO-5H-[1,3]THIAZOLO[3,2-A]PYRIDINE-3-CARBOXYLIC+ACID'>XC2</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n0l|1n0l]], [[1pdk|1pdk]], [[1qpp|1qpp]], [[1qpx|1qpx]], [[2j2z|2j2z]], [[3dpa|3dpa]]</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=2j7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j7l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j7l RCSB], [http://www.ebi.ac.uk/pdbsum/2j7l 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/j7/2j7l_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 == | |||
A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by approximately 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone-subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors. | |||
Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria.,Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenstrom M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17897-902. Epub 2006 Nov 10. PMID:17098869<ref>PMID:17098869</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Almqvist, F.]] | [[Category: Almqvist, F.]] | ||
Revision as of 12:14, 30 September 2014
E.COLI P PILUS CHAPERONE PAPD IN COMPLEX WITH A PILUS BIOGENESIS INHIBITOR, PILICIDE 2CE.COLI P PILUS CHAPERONE PAPD IN COMPLEX WITH A PILUS BIOGENESIS INHIBITOR, PILICIDE 2C
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either type 1 or P pili, adherence to bladder cells, and biofilm formation mediated by type 1 pili were all reduced by approximately 90% in laboratory and clinical E. coli strains. The structure of the pilicide bound to the P pilus chaperone PapD revealed that the pilicide bound to the surface of the chaperone known to interact with the usher, the outer-membrane assembly platform where pili are assembled. Point mutations in the pilicide-binding site dramatically reduced pilus formation but did not block the ability of PapD to bind subunits and mediate their folding. Surface plasmon resonance experiments confirmed that the pilicide interfered with the binding of chaperone-subunit complexes to the usher. These pilicides thus target key virulence factors in pathogenic bacteria and represent a promising proof of concept for developing drugs that function by targeting virulence factors. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria.,Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenstrom M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17897-902. Epub 2006 Nov 10. PMID:17098869[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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