THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria

Nature Microbiology

Volumn 1, Issue 2, 2016, Pages

  Cox, Jonathan A G ^a   Abrahams, Katherine A ^a   Alemparte, Carlos ^b   Ghidelli Disse, Sonja ^c   Rullas, Joaquín ^b   Angulo Barturen, Iñigo ^b   Singh, Albel ^a   Gurcha, Sudagar S ^a   Nataraj, Vijayashankar ^a   Bethell, Stephen ^a   Remuiñán, Modesto J ^b   Encinas, Lourdes ^b   Jervis, Peter J ^a   Cammack, Nicholas C ^b   Bhatt, Apoorva ^a   Kruse, Ulrich ^c   Bantscheff, Marcus ^c   Fütterer, Klaus ^a   Barros, David ^b   Ballell, Lluis ^b   Drewes, Gerard ^c   Besra, Gurdyal S ^a   more..

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b GLAXOSMITHKLINE   (Spain)

^c GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMYCOBACTERIAL AGENT; ENOYL COENZYME A HYDRATASE; FATTY ACID SYNTHASE; FATTY ACID SYNTHASE II; LONG CHAIN FATTY ACID; MYCOLIC ACID; PROTEIN ECHA6; TETRAHYDROPYRAZO[1,5 A]PYRIMIDINE 3 CARBOXAMIDE; UNCLASSIFIED DRUG; BACTERIAL PROTEIN; ESSENTIAL FATTY ACID; FATTY ACID BINDING PROTEIN; PROTEIN BINDING; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; TUBERCULOSTATIC AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERICIDAL ACTIVITY; BINDING AFFINITY; BINDING COMPETITION; CONTROLLED STUDY; DRUG BINDING; FATTY ACID TRANSPORT; FEMALE; IN VITRO STUDY; IN VIVO STUDY; LIGAND BINDING; MINIMUM INHIBITORY CONCENTRATION; MOUSE; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; STEREOSPECIFICITY; TUBERCULOSIS; ANIMAL; DISEASE MODEL; DRUG EFFECTS; ESSENTIAL GENE; GENETICS; METABOLISM; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; MISSENSE MUTATION; MYCOBACTERIUM TUBERCULOSIS; PATHOLOGY; PROTEIN ANALYSIS; TWO HYBRID SYSTEM;

ANIMALS; ANTITUBERCULAR AGENTS; BACTERIAL PROTEINS; DISEASE MODELS, ANIMAL; FATTY ACID-BINDING PROTEINS; FATTY ACIDS, ESSENTIAL; GENES, ESSENTIAL; MICE; MICROBIAL SENSITIVITY TESTS; MUTATION, MISSENSE; MYCOBACTERIUM TUBERCULOSIS; POINT MUTATION; PROTEIN BINDING; PROTEIN INTERACTION MAPPING; PYRAZOLES; PYRIMIDINES; TUBERCULOSIS; TWO-HYBRID SYSTEM TECHNIQUES;

EID: 84962300370     PISSN: None     EISSN: 20585276     Source Type: Journal    
DOI: 10.1038/nmicrobiol.2015.6     Document Type: Article

References (42)

1. WHO. Global Tuberculosis Report 2013 (World Health Organization, 2013).
2. Abrahams, K. A. et al. Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB. PLoS ONE 7, e52951 (2012).
3. Gurcha, S. S. et al. Biochemical and structural characterization of mycobacterial aspartyl-tRNA synthetase AspS, a promising TB drug target. PLoS ONE 9, e113568 (2014).
4. Mugumbate, G. et al. Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation. PLoS ONE 10, e0121492 (2015).
5. Wang, F. et al. Identification of a small molecule with activity against drugresistant and persistent tuberculosis. Proc. Natl Acad. Sci. USA 110, E2510-E2517 (2013).
6. Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223-227 (2005).
7. Grzegorzewicz, A. E. et al. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nature Chem. Biol. 8, 334-341 (2012).
8. La Rosa, V. et al. MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. Antimicrob. Agents Chemother. 56, 324-331 (2012).
9. Li, K. et al. Multitarget drug discovery for tuberculosis and other infectious diseases. J. Med. Chem. 57, 3126-3139 (2014).
10. Li,W. et al. Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 58, 6413-6423 (2014).
11. Rao, S. P. et al. Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis. Sci. Transl. Med. 5, 214ra168 (2013).
12. Remuinan, M. J. et al. Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6′,7′-dihydrospiro[piperidine-4,4′-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3. PLoS ONE 8, e60933 (2013).
13. Tahlan, K. et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacteriumtuberculosis. Antimicrob. Agents Chemother. 56, 1797-1809 (2012).
14. Banerjee, A. et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 263, 227-230 (1994).
15. Zhang, Y., Heym, B., Allen, B., Young, D. & Cole, S. The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature 358, 591-593 (1992).
16. Bantscheff, M. et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nature Biotechnol. 29, 255-265 (2011).
17. Brown, A. K. et al. Identification of the dehydratase component of the mycobacterial mycolic acid-synthesizing fatty acid synthase-II complex. Microbiology 153, 4166-4173 (2007).
18. Rana, A. K. et al. Ppm1-encoded polyprenyl monophosphomannose synthase activity is essential for lipoglycan synthesis and survival in mycobacteria. PLoS ONE 7, e48211 (2012).
19. Kremer, L. et al. Thiolactomycin and related analogues as novel antimycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J. Biol. Chem. 275, 16857-16864 (2000).
20. Cantaloube, S., Veyron-Churlet, R., Haddache, N., Daffe, M. & Zerbib, D. The Mycobacterium tuberculosis FAS-II dehydratases and methyltransferases define the specificity of the mycolic acid elongation complexes. PLoS ONE 6, e29564 (2011).
21. Bahnson, B. J., Anderson, V. E. & Petsko, G. A. Structural mechanism of enoyl-CoA hydratase: three atoms from a single water are added in either an E1cb stepwise or concerted fashion. Biochemistry 41, 2621-2629 (2002).
22. Rullas, J. et al. Fast standardized therapeutic-efficacy assay for drug discovery against tuberculosis. Antimicrob. Agents Chemother. 54, 2262-2264 (2010).
23. Engel, C. K., Mathieu, M., Zeelen, J. P., Hiltunen, J. K. & Wierenga, R. K. Crystal structure of enoyl-coenzyme A (CoA) hydratase at 2.5 angstroms resolution: a spiral fold defines the CoA-binding pocket. EMBO J. 15, 5135-5145 (1996).
24. Hamed, R. B., Batchelar, E. T., Clifton, I. J. & Schofield, C. J. Mechanisms and structures of crotonase superfamily enzymes-how nature controls enolate and oxyanion reactivity. Cell. Mol. Life Sci. 65, 2507-2527 (2008).
25. Holm, L. & Rosenstrom, P. Dali server: conservation mapping in 3D. Nucleic Acids Res. 38, W545-W549 (2010).
26. Hazbon, M. H. et al. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 50, 2640-2649 (2006).
27. Cole, S. T. et al. Massive gene decay in the leprosy bacillus. Nature 409, 1007-1011 (2001).
28. Sassetti, C. M., Boyd, D. H. & Rubin, E. J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48, 77-84 (2003).
29. Franceschini, A. et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41, D808-D815 (2013).
30. Kremer, L. et al. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem. J. 364, 423-430 (2002).
31. Besra, G. S. et al. Identification of the apparent carrier in mycolic acid synthesis. Proc. Natl Acad. Sci. USA 91, 12735-12739 (1994).
32. Hu, Y. et al. 3-Ketosteroid 9α-hydroxylase is an essential factor in the pathogenesis of Mycobacterium tuberculosis. Mol. Microbiol. 75, 107-121 (2010).
33. Karimova, G., Pidoux, J., Ullmann, A. & Ladant, D. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc. Natl Acad. Sci. USA 95, 5752-5756 (1998).
34. Savitski, M. M. et al. Targeted data acquisition for improved reproducibility and robustness of proteomic mass spectrometry assays. J. Am. Soc. Mass Spectr. 21, 1668-1679 (2010).
35. Savitski, M. M. et al. Measuring and managing ratio compression for accurate iTRAQ/TMT quantification. J. Proteome Res. 12, 3586-3598 (2013).
36. Savitski, M. M. et al. Delayed fragmentation and optimized isolation width settings for improvement of protein identification and accuracy of isobaric mass tag quantification on Orbitrap-type mass spectrometers. Anal. Chem. 83, 8959-8967 (2011).
37. Kabsch, W. XDS. Acta Crystallogr. D 66, 125-132 (2010).
38. CCP4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).
39. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
40. Emsley, P., Lohkamp, B., Scott,W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486-501 (2010).
41. Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240-255 (1997).
42. Adams, P. D. et al. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D 58, 1948-1954 (2002).