5i7n: Difference between revisions
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==MaoC-like dehydratase== | ==MaoC-like dehydratase== | ||
<StructureSection load='5i7n' size='340' side='right' caption='[[5i7n]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='5i7n' size='340' side='right'caption='[[5i7n]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5i7n]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7N OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5i7n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I7N FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5i7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7n OCA], [https://pdbe.org/5i7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i7n RCSB], [https://www.ebi.ac.uk/pdbsum/5i7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7n ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B1MM63_MYCA9 B1MM63_MYCA9] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, abscesses, and rapid larval death. Generating a cord-deficient Mabs mutant would allow us to address the contribution of cording in the physiopathological signs of the R variant. Herein, a deletion mutant of MAB_4780, encoding a dehydratase, distinct from the beta-hydroxyacyl-ACP dehydratase HadABC complex, was constructed in the R morphotype. This mutant exhibited an alteration of the mycolic acid composition and a pronounced defect in cording. This correlated with an extremely attenuated phenotype not only in wild-type but also in immunocompromised zebrafish embryos lacking either macrophages or neutrophils. The abolition of granuloma formation in embryos infected with the dehydratase mutant was associated with a failure to replicate in macrophages, presumably due to limited inhibition of the phagolysosomal fusion. Overall, these results indicate that MAB_4780 is required for Mabs to successfully establish acute and lethal infections. Therefore, targeting MAB_4780 may represent an attractive antivirulence strategy to control Mabs infections, refractory to most standard chemotherapeutic interventions. The combination of a dehydratase assay with a high-resolution crystal structure of MAB_4780 opens the way to identify such specific inhibitors. | |||
Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.,Halloum I, Carrere-Kremer S, Blaise M, Viljoen A, Bernut A, Le Moigne V, Vilcheze C, Guerardel Y, Lutfalla G, Herrmann JL, Jacobs WR Jr, Kremer L Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4228-37. doi:, 10.1073/pnas.1605477113. Epub 2016 Jul 6. PMID:27385830<ref>PMID:27385830</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5i7n" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacteroides abscessus]] | ||
[[Category: | [[Category: Blaise M]] | ||
