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''' | ==Crystal structure of E.Coli DsbA soaked with compound 4== | ||
<StructureSection load='4wf5' size='340' side='right' caption='[[4wf5]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4wf5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli_bl21(de3) Escherichia coli bl21(de3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WF5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WF5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=WF4:4-METHYL-2-[4-(TRIFLUOROMETHYL)PHENYL]-1,3-THIAZOLE-5-CARBOXYLIC+ACID'>WF4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fvk|1fvk]], [[4wey|4wey]], [[4wf4|4wf4]], [[4wet|4wet]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-disulfide_reductase_(glutathione) Protein-disulfide reductase (glutathione)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.4.2 1.8.4.2] </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=4wf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wf5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wf5 RCSB], [http://www.ebi.ac.uk/pdbsum/4wf5 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The thiol-disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram-negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell-based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence. | |||
Application of Fragment-Based Screening to the Design of Inhibitors of Escherichia coli DsbA.,Adams LA, Sharma P, Mohanty B, Ilyichova OV, Mulcair MD, Williams ML, Gleeson EC, Totsika M, Doak BC, Caria S, Rimmer K, Horne J, Shouldice SR, Vazirani M, Headey SJ, Plumb BR, Martin JL, Heras B, Simpson JS, Scanlon MJ Angew Chem Int Ed Engl. 2014 Dec 30. doi: 10.1002/anie.201410341. PMID:25556635<ref>PMID:25556635</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Doak, B | </StructureSection> | ||
[[Category: | [[Category: Adams, L A]] | ||
[[Category: | [[Category: Caria, S]] | ||
[[Category: Doak, B C]] | |||
[[Category: Gleeson, E C]] | |||
[[Category: Headey, S J]] | |||
[[Category: Heras, B]] | [[Category: Heras, B]] | ||
[[Category: Ilyichova, O V]] | |||
[[Category: Martin, J L]] | |||
[[Category: Mohanty, B]] | |||
[[Category: Mulcair, M D]] | |||
[[Category: Plumb, B R]] | |||
[[Category: Rimmer, K]] | [[Category: Rimmer, K]] | ||
[[Category: Scanlon, M J]] | |||
[[Category: Sharma, P]] | [[Category: Sharma, P]] | ||
[[Category: | [[Category: Shouldice, S R]] | ||
[[Category: Simpson, J S]] | |||
[[Category: Totsika, M]] | |||
[[Category: Vazirani, M]] | [[Category: Vazirani, M]] | ||
[[Category: | [[Category: Williams, M L]] | ||
[[Category: Disulfide oxidoreductase]] | |||
[[Category: Dsba]] | |||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | |||
[[Category: Redox protein]] | |||
[[Category: | |||
[[Category: | |||
[[Category: | |||
[[Category: | |||
Revision as of 19:51, 21 January 2015
Crystal structure of E.Coli DsbA soaked with compound 4Crystal structure of E.Coli DsbA soaked with compound 4
Structural highlights
Publication Abstract from PubMedThe thiol-disulfide oxidoreductase enzyme DsbA catalyzes the formation of disulfide bonds in the periplasm of Gram-negative bacteria. DsbA substrates include proteins involved in bacterial virulence. In the absence of DsbA, many of these proteins do not fold correctly, which renders the bacteria avirulent. Thus DsbA is a critical mediator of virulence and inhibitors may act as antivirulence agents. Biophysical screening has been employed to identify fragments that bind to DsbA from Escherichia coli. Elaboration of one of these fragments produced compounds that inhibit DsbA activity in vitro. In cell-based assays, the compounds inhibit bacterial motility, but have no effect on growth in liquid culture, which is consistent with selective inhibition of DsbA. Crystal structures of inhibitors bound to DsbA indicate that they bind adjacent to the active site. Together, the data suggest that DsbA may be amenable to the development of novel antibacterial compounds that act by inhibiting bacterial virulence. Application of Fragment-Based Screening to the Design of Inhibitors of Escherichia coli DsbA.,Adams LA, Sharma P, Mohanty B, Ilyichova OV, Mulcair MD, Williams ML, Gleeson EC, Totsika M, Doak BC, Caria S, Rimmer K, Horne J, Shouldice SR, Vazirani M, Headey SJ, Plumb BR, Martin JL, Heras B, Simpson JS, Scanlon MJ Angew Chem Int Ed Engl. 2014 Dec 30. doi: 10.1002/anie.201410341. PMID:25556635[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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