4mcu: Difference between revisions
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==Crystal structure of disulfide oxidoreductase from Klebsiella pneumoniae in reduced state== | |||
<StructureSection load='4mcu' size='340' side='right' caption='[[4mcu]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4mcu]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Klep3 Klep3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MCU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MCU FirstGlance]. <br> | |||
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dsbA, KPK_5512 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=507522 KLEP3])</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=4mcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mcu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mcu RCSB], [http://www.ebi.ac.uk/pdbsum/4mcu PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacterial DsbA enzymes catalyze oxidative folding of virulence factors, and have been identified as targets for antivirulence drugs. However, DsbA enzymes characterized to date exhibit a wide spectrum of redox properties and divergent structural features compared to the prototypical DsbA enzyme of Escherichia coli DsbA (EcDsbA). Nonetheless, sequence analysis shows that DsbAs are more highly conserved than their known substrate virulence factors, highlighting the potential to inhibit virulence across a range of organisms by targeting DsbA. For example, Salmonella enterica typhimurium (SeDsbA, 86 % sequence identity to EcDsbA) shares almost identical structural, surface and redox properties. Using comparative sequence and structure analysis we predicted that five other bacterial DsbAs would share these properties. To confirm this, we characterized Klebsiella pneumoniae DsbA (KpDsbA, 81 % identity to EcDsbA). As expected, the redox properties, structure and surface features (from crystal and NMR data) of KpDsbA were almost identical to those of EcDsbA and SeDsbA. Moreover, KpDsbA and EcDsbA bind peptides derived from their respective DsbBs with almost equal affinity, supporting the notion that compounds designed to inhibit EcDsbA will also inhibit KpDsbA. Taken together, our data show that DsbAs fall into different classes; that DsbAs within a class may be predicted by sequence analysis of binding loops; that DsbAs within a class are able to complement one another in vivo and that compounds designed to inhibit EcDsbA are likely to inhibit DsbAs within the same class. | |||
Comparative Sequence, Structure and Redox Analyses of Klebsiella pneumoniae DsbA Show That Anti-Virulence Target DsbA Enzymes Fall into Distinct Classes.,Kurth F, Rimmer K, Premkumar L, Mohanty B, Duprez W, Halili MA, Shouldice SR, Heras B, Fairlie DP, Scanlon MJ, Martin JL PLoS One. 2013 Nov 14;8(11):e80210. doi: 10.1371/journal.pone.0080210. PMID:24244651<ref>PMID:24244651</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: Kurth, F | == References == | ||
[[Category: Martin, J L | <references/> | ||
[[Category: Premkumar, L | __TOC__ | ||
</StructureSection> | |||
[[Category: Klep3]] | |||
[[Category: Kurth, F]] | |||
[[Category: Martin, J L]] | |||
[[Category: Premkumar, L]] | |||
[[Category: Disulfide oxidase]] | [[Category: Disulfide oxidase]] | ||
[[Category: Dsba]] | [[Category: Dsba]] | ||
Revision as of 21:51, 21 December 2014
Crystal structure of disulfide oxidoreductase from Klebsiella pneumoniae in reduced stateCrystal structure of disulfide oxidoreductase from Klebsiella pneumoniae in reduced state
Structural highlights
Publication Abstract from PubMedBacterial DsbA enzymes catalyze oxidative folding of virulence factors, and have been identified as targets for antivirulence drugs. However, DsbA enzymes characterized to date exhibit a wide spectrum of redox properties and divergent structural features compared to the prototypical DsbA enzyme of Escherichia coli DsbA (EcDsbA). Nonetheless, sequence analysis shows that DsbAs are more highly conserved than their known substrate virulence factors, highlighting the potential to inhibit virulence across a range of organisms by targeting DsbA. For example, Salmonella enterica typhimurium (SeDsbA, 86 % sequence identity to EcDsbA) shares almost identical structural, surface and redox properties. Using comparative sequence and structure analysis we predicted that five other bacterial DsbAs would share these properties. To confirm this, we characterized Klebsiella pneumoniae DsbA (KpDsbA, 81 % identity to EcDsbA). As expected, the redox properties, structure and surface features (from crystal and NMR data) of KpDsbA were almost identical to those of EcDsbA and SeDsbA. Moreover, KpDsbA and EcDsbA bind peptides derived from their respective DsbBs with almost equal affinity, supporting the notion that compounds designed to inhibit EcDsbA will also inhibit KpDsbA. Taken together, our data show that DsbAs fall into different classes; that DsbAs within a class may be predicted by sequence analysis of binding loops; that DsbAs within a class are able to complement one another in vivo and that compounds designed to inhibit EcDsbA are likely to inhibit DsbAs within the same class. Comparative Sequence, Structure and Redox Analyses of Klebsiella pneumoniae DsbA Show That Anti-Virulence Target DsbA Enzymes Fall into Distinct Classes.,Kurth F, Rimmer K, Premkumar L, Mohanty B, Duprez W, Halili MA, Shouldice SR, Heras B, Fairlie DP, Scanlon MJ, Martin JL PLoS One. 2013 Nov 14;8(11):e80210. doi: 10.1371/journal.pone.0080210. PMID:24244651[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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