5I7N

MaoC-like dehydratase

Summary for 5I7N

• Entry DOI: 10.2210/pdb5i7n/pdb
• Descriptor: MaoC-like dehydratase (2 entities in total)
• Functional Keywords: enzyme, hydratase, maoc like, lyase
• Biological source: Mycobacterium abscessus
• Total number of polymer chains: 1
• Total formula weight: 36672.25

Authors

Blaise, M. (deposition date: 2016-02-18, release date: 2016-07-06, Last modification date: 2024-11-20)

Primary citation

Halloum, I.,Carrere-Kremer, S.,Blaise, M.,Viljoen, A.,Bernut, A.,Le Moigne, V.,Vilcheze, C.,Guerardel, Y.,Lutfalla, G.,Herrmann, J.L.,Jacobs, W.R.,Kremer, L.
Deletion of a dehydratase important for intracellular growth and cording renders rough Mycobacterium abscessus avirulent.
Proc.Natl.Acad.Sci.USA, 113:E4228-E4237, 2016

PubMed Abstract: 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 β-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.

PubMed: 27385830
DOI: 10.1073/pnas.1605477113

Experimental method

X-RAY DIFFRACTION (1.65 Å)