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Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.

Zhang L, Zhao Y, Gao Y, Wu L, Gao R, Zhang Q, Wang Y, Wu C, Wu F, Gurcha SS, Veerapen N, Batt SM, Zhao W, Qin L, Yang X, Wang M, Zhu Y, Zhang B, Bi L, Zhang X, Yang H, Guddat LW, Xu W, Wang Q, Li J, Besra GS, Rao Z
Science 368 1211-1219 (2020)
Related entries: 7bve, 7bvf, 7bvg, 7bvh

Cited: 43 times
EuropePMC logo PMID: 32327601

Abstract

The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as targets for the anti-tuberculosis drug ethambutol. In this study, we determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits arabinosyltransferases by binding to the same site as both substrates in EmbB and EmbC. Most drug-resistant mutations are located near the ethambutol binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and the development of new anti-tuberculosis agents.

Reviews - 7bvc mentioned but not cited (2)

  1. Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall. Batt SM, Burke CE, Moorey AR, Besra GS. Cell Surf 6 100044 (2020)
  2. Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM. Bendre AD, Peters PJ, Kumar J. J Membr Biol 254 321-341 (2021)


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  1. Mechanisms of Drug-Induced Tolerance in Mycobacterium tuberculosis. Goossens SN, Sampson SL, Van Rie A. Clin Microbiol Rev 34 e00141-20 (2020)
  2. Mycobacterium smegmatis: The Vanguard of Mycobacterial Research. Sparks IL, Derbyshire KM, Jacobs WR, Morita YS. J Bacteriol 205 e0033722 (2023)
  3. The Struggle to End a Millennia-Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis. Edwards BD, Field SK. Drugs 82 1695-1715 (2022)
  4. Anti-tuberculosis drug development via targeting the cell envelope of Mycobacterium tuberculosis. Xu X, Dong B, Peng L, Gao C, He Z, Wang C, Zeng J. Front Microbiol 13 1056608 (2022)
  5. Cell Surface Biosynthesis and Remodeling Pathways in Mycobacteria Reveal New Drug Targets. Shaku M, Ealand C, Kana BD. Front Cell Infect Microbiol 10 603382 (2020)
  6. Genetic polymorphism related to ethambutol outcomes and susceptibility to toxicity. Barliana MI, Afifah NN, Yunivita V, Ruslami R. Front Genet 14 1118102 (2023)
  7. Unraveling the mechanisms of intrinsic drug resistance in Mycobacterium tuberculosis. Poulton NC, Rock JM. Front Cell Infect Microbiol 12 997283 (2022)
  8. Mycobacterium tuberculosis: Pathogenesis and therapeutic targets. Yang J, Zhang L, Qiao W, Luo Y. MedComm (2020) 4 e353 (2023)
  9. Drug-resistant strains of Mycobacterium tuberculosis: cell envelope profiles and interactions with the host. Schami A, Islam MN, Belisle JT, Torrelles JB. Front Cell Infect Microbiol 13 1274175 (2023)
  10. Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection. Italia A, Shaik MM, Peri F. Biomolecules 13 999 (2023)
  11. Mycobacterium tuberculosis and its clever approaches to escape the deadly macrophage. Krishnan V, Nath S, Nair P, Das B. World J Microbiol Biotechnol 39 300 (2023)
  12. Pharmacologic Management of Mycobacterium chimaera Infections: A Primer for Clinicians. Mason M, Gregory E, Foster K, Klatt M, Zoubek S, Eid AJ. Open Forum Infect Dis 9 ofac287 (2022)
  13. Protein N-glycosylation and O-mannosylation are catalyzed by two evolutionarily related GT-C glycosyltransferases. Bai L, Li H. Curr Opin Struct Biol 68 66-73 (2021)
  14. Target Identification in Anti-Tuberculosis Drug Discovery. Capela R, Félix R, Clariano M, Nunes D, Perry MJ, Lopes F. Int J Mol Sci 24 10482 (2023)

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  2. Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria. Chen X, Chen J, Yan B, Zhang W, Guddat LW, Liu X, Rao Z. Proc Natl Acad Sci U S A 117 16324-16332 (2020)
  3. Biosynthetic Glycan Labeling. Marando VM, Kim DE, Calabretta PJ, Kraft MB, Bryson BD, Kiessling LL. J Am Chem Soc 143 16337-16342 (2021)
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  7. mbtD and celA1 association with ethambutol resistance in Mycobacterium tuberculosis: A multiomics analysis. Wu Z, Tan Q, Zhang C, Zhao Y, Liao Q, Yu M, Xu L, Wang J, Liang H, Li H, Chen L, Chen X, Wei W. Front Cell Infect Microbiol 12 959911 (2022)
  8. A Protective Role of Coenzyme Q10 in Ethambutol-Induced Retinal Ganglion Cell Toxicity: A Randomised Controlled Trial in Mice. Irma J, Kartika A, Rini M, Setiohadji B, Salim J. Neuroophthalmology 46 298-303 (2022)
  9. Application of combined CRISPR screening for genetic and chemical-genetic interaction profiling in Mycobacterium tuberculosis. Yan MY, Zheng D, Li SS, Ding XY, Wang CL, Guo XP, Zhan L, Jin Q, Yang J, Sun YC. Sci Adv 8 eadd5907 (2022)
  10. Arabinogalactan enhances Mycobacterium marinum virulence by suppressing host innate immune responses. Li YY, Liu HM, Wang D, Lu Y, Ding C, Zhou LS, Wu XY, Zhou ZW, Xu SQ, Lin C, Qin LH, Li Y, Liu J, Liu HP, Zhang L. Front Immunol 13 879775 (2022)
  11. Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus. Wang S, Cai X, Yu W, Zeng S, Zhang J, Guo L, Gao Y, Lu Z, Hameed HMA, Fang C, Tian X, Yusuf B, Chhotaray C, Alam MDS, Zhang B, Ge H, Maslov DA, Cook GM, Peng J, Lin Y, Zhong N, Zhang G, Zhang T. Microbiol Spectr 10 e0276321 (2022)
  12. Based on Transcriptome Sequencing of Cell Wall Deficient Strain, Research on Arabinosyltransferase Inhibition's Effect on the Synthesis of Cell Wall in Chlamydomonas reinhardtii. Zhang W, Shang M, Qiu L, Liu B, Zang X. Int J Mol Sci 24 17595 (2023)
  13. Computational modeling and bioinformatic analyses of functional mutations in drug target genes in Mycobacterium tuberculosis. Singh P, Jamal S, Ahmed F, Saqib N, Mehra S, Ali W, Roy D, Ehtesham NZ, Hasnain SE. Comput Struct Biotechnol J 19 2423-2446 (2021)
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  15. Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2. Zhang L, Zhao Y, Gao R, Li J, Yang X, Gao Y, Zhao W, Gurcha SS, Veerapen N, Batt SM, Besra KK, Xu W, Bi L, Zhang X, Guddat LW, Yang H, Wang Q, Besra GS, Rao Z. Protein Cell 11 505-517 (2020)
  16. Cryo-EM structure of arabinosyltransferase EmbB from Mycobacterium smegmatis. Tan YZ, Rodrigues J, Keener JE, Zheng RB, Brunton R, Kloss B, Giacometti SI, Rosário AL, Zhang L, Niederweis M, Clarke OB, Lowary TL, Marty MT, Archer M, Potter CS, Carragher B, Mancia F. Nat Commun 11 3396 (2020)
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  25. Structure and Function of Mycobacterial Arabinofuranosyltransferases. Tan YZ, Mancia F. Subcell Biochem 99 379-391 (2022)
  26. Structure of the priming arabinosyltransferase AftA required for AG biosynthesis of Mycobacterium tuberculosis. Gong Y, Wei C, Wang J, Mu N, Lu Q, Wu C, Yan N, Yang H, Zhao Y, Yang X, Gurcha SS, Veerapen N, Batt SM, Hao Z, Da L, Besra GS, Rao Z, Zhang L. Proc Natl Acad Sci U S A 120 e2302858120 (2023)
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