Structural and functional elucidation of yeast lanosterol 14α-demethylase in complex with Agrochemical antifungals

PLoS ONE

Volumn 11, Issue 12, 2016, Pages

  Tyndall, Joel D A ^a   Sabherwal, Manya ^b   Sagatova, Alia A ^b   Keniya, Mikhail V ^a,b   Negroni, Jacopo ^c   Wilson, Rajni K ^b   Woods, Matthew A ^b   Tietjen, Klaus ^c   Monk, Brian C ^a,b  

^a UNIVERSITY OF OTAGO   (New Zealand)

^b UNIVERSITY OF OTAGO   (New Zealand)

^c BAYER AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AGRICULTURAL CHEMICAL; ANTIFUNGAL AGENT; DIFENOCONAZOLE; EPOXICONAZOLE; FLUQUINCONAZOLE; FUNGICIDE; MEMBRANE PROTEIN; OXO PROTHIOCONAZOLE; PROCHLORAZ; PROTHIOCONAZOLE; STEROL 14ALPHA DEMETHYLASE; STEROL 14ALPHA DEMETHYLASE INHIBITOR; TEBUCONAZOLE; UNCLASSIFIED DRUG; PROTEIN BINDING; PYRROLE DERIVATIVE;

ANTIFUNGAL ACTIVITY; ARTICLE; ASPERGILLUS FUMIGATUS; BINDING AFFINITY; CANDIDA ALBICANS; CANDIDA GLABRATA; CONTROLLED STUDY; DRUG BINDING SITE; ENANTIOMER; ENZYME ACTIVITY; ENZYME BINDING; ENZYME STRUCTURE; FUNGUS MUTATION; NONHUMAN; PROTEIN EXPRESSION; RACEMIC MIXTURE; SACCHAROMYCES CEREVISIAE; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG EFFECTS; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; ENZYMOLOGY; METABOLISM; MICROBIAL SENSITIVITY TEST; STRUCTURE ACTIVITY RELATION; YEAST;

14-ALPHA DEMETHYLASE INHIBITORS; AGROCHEMICALS; ANTIFUNGAL AGENTS; AZOLES; BINDING SITES; CATALYTIC DOMAIN; MICROBIAL SENSITIVITY TESTS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PROTEIN BINDING; SACCHAROMYCES CEREVISIAE; STEROL 14-DEMETHYLASE; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; YEASTS;

EID: 85000399585     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0167485     Document Type: Article

References (45)

1. Russell PE. A century of fungicide evolution. J Agri Sci 143(1):11-25.
2. Bowyer P, Denning DW. Environmental fungicides and triazole resistance in Aspergillus. Pest Manag Sci. 2014; 70(2):173-8. doi: 10.1002/ps.3567 PMID: 23616354
3. Bhanderi BB, Yadav MM, Roy A. Antifungal Drug Resistance, Concerns for Veterinarians. Vet World. 2009; 2(5):204-7.
4. Kuck K-H, Stenzel K, Vors J-P. Sterol Biosynthesis Inhibitors. In: Kraemer W, editor. Modern Crop Protection Compounds 1-3. 2nd ed. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2012.
5. Parker JE, Warrilow AG, Price CL, Mullins JG, Kelly DE, Kelly SL. Resistance to antifungals that target CYP51. J Chem Biol. 2014; 7(4):143-61. doi: 10.1007/s12154-014-0121-1 PMID: 25320648
6. Price CL, Parker JE, Warrilow AG, Kelly DE, Kelly SL. Azole fungicides, understanding resistance mechanisms in agricultural fungal pathogens. Pest Manag Sci. 2015; 71(8):1054-8. doi: 10.1002/ps. 4029 PMID: 25914201
7. Tietjen K. Contribution of plant responses to efficacy of fungicides, A perspective. In: Deising HB, B. F, A. M, E.C. O, H. S, G. S, editors. Modern Fungicides and Antifungal Compounds. VIII. (Submitted) 2016.
8. Snelders E, Karawajczyk A, Verhoeven RJ, Venselaar H, Schaftenaar G, Verweij PE, et al. The structure-function relationship of the Aspergillus fumigatus cyp51A L98H conversion by site-directed mutagenesis: The mechanism of L98H azole resistance. Fungal Genet Biol. 2011; 48(11):1062-70. doi: 10. 1016/j.fgb.2011.08.002 PMID: 21907818
9. Chowdhary A, Kathuria S, Xu J, Meis JF. Emergence of azole-resistant Aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS pathogens. 2013; 9 (10):e1003633. doi: 10.1371/journal.ppat.1003633 PMID: 24204249
10. van der Linden JW, Camps SM, Kampinga GA, Arends JP, Debets-Ossenkopp YJ, Haas PJ, et al. Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles. Clin Infect Dis. 2013; 57(4):513-20. doi: 10.1093/cid/cit320 PMID: 23667263
11. Camps SM, Rijs AJ, Klaassen CH, Meis JF, O'Gorman CM, Dyer PS, et al. Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism. J Clin Microbiol. 2012; 50(8):2674-80. doi: 10.1128/JCM.00335-12 PMID: 22675126
12. Verweij PE, Chowdhary A, Melchers WJ, Meis JF. Azole resistance in Aspergillus fumigatus: can we retain the clinical use of mold-active antifungal azoles? Clin Infect Dis. 2016; 62(3):362-8. doi: 10.1093/cid/civ885 PMID: 26486705
13. Franceschini S, Chitarra W, Pugliese M, Gisi U, Garibaldi A, Gullino ML. Quantification of Aspergillus fumigatus and enteric bacteria in European compost and biochar. Compost Sci Util. 2016; 24(1):20-9.
14. Kjaerstad MB, Taxvig C, Nellemann C, Vinggaard AM, Andersen HR. Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals. Reprod Toxicol. 2010; 30 (4):573-82. doi: 10.1016/j.reprotox.2010.07.009 PMID: 20708073
15. Trosken E-R. Toxicological Evaluation of Azole Fungicides in Agriculture and Food Chemistry: University Wurzburg, Germany; 2005.
16. Chen ZF, Ying GG. Occurrence, fate and ecological risk of five typical azole fungicides as therapeutic and personal care products in the environment: A review. Environ Int. 2015; 84:142-53. doi: 10.1016/j. envint.2015.07.022 PMID: 26277639
17. Reif DM, Martin MT, Tan SW, Houck KA, Judson RS, Richard AM, et al. Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect. 2010; 118(12):1714-20. doi: 10.1289/ehp.1002180 PMID: 20826373
18. Becher R, Wirsel SG. Fungal cytochrome P450 sterol 14alpha-demethylase (CYP51) and azole resistance in plant and human pathogens. Appl Microbiol Biotechnol. 2012; 95(4):825-40. doi: 10.1007/s00253-012-4195-9 PMID: 22684327
19. Mullins JG, Parker JE, Cools HJ, Togawa RC, Lucas JA, Fraaije BA, et al. Molecular modelling of the emergence of azole resistance in Mycosphaerella graminicola. PLoS One. 2011; 6(6):e20973. doi: 10.1371/journal.pone.0020973 PMID: 21738598
20. Monk BC, Tomasiak TM, Keniya MV, Huschmann FU, Tyndall JD, O'Connell JD 3rd, et al. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proc Natl Acad Sci U S A. 2014; 111(10):3865-70. doi: 10.1073/pnas.1324245111 PMID: 24613931
21. Sagatova AA, Keniya MV, Wilson RK, Monk BC, Tyndall JD. Structural Insights into Binding of the Antifungal Drug Fluconazole to Saccharomyces cerevisiae Lanosterol 14alpha-Demethylase. Antimicrob Agents Chemother. 2015; 59(8):4982-9. doi: 10.1128/AAC.00925-15 PMID: 26055382
22. Sagatova AA, Keniya MV, Wilson RK, Sabherwal M, Tyndall JD, Monk BC. Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14alpha-demethylase. Scientific reports. 2016; 6:26213. doi: 10.1038/srep26213 PMID: 27188873
23. Mo C, Bard M. A systematic study of yeast sterol biosynthetic protein-protein interactions using the split-ubiquitin system. Biochim Biophys Acta. 2005; 1737(2-3):152-60. doi: 10.1016/j.bbalip.2005.11. 002 PMID: 16300994
24. Price CL, Warrilow AG, Parker JE, Mullins JG, Nes WD, Kelly DE, et al. Novel Substrate Specificity and Temperature-Sensitive Activity of Mycosphaerella graminicola CYP51 Supported by the Native NADPH Cytochrome P450 Reductase. Applied and environmental microbiology. 2015; 81(10):3379-86. doi: 10.1128/AEM.03965-14 PMID: 25746994
25. Lamping E, Monk BC, Niimi K, Holmes AR, Tsao S, Tanabe K, et al. Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae. Eukaryot Cell. 2007; 6(7):1150-65. doi: 10.1128/EC.00091-07 PMID: 17513564
26. Haas M, Justus K. Metabolism of Prothioconazole (JAU6476) in animals and plants. Pflanzenschutz-Nachr Bayer. 2004; 57(2):207-24.
27. Parker JE, Warrilow AG, Cools HJ, Fraaije BA, Lucas JA, Rigdova K, et al. Prothioconazole and prothioconazole-desthio activities against Candida albicans sterol 14-alpha-demethylase. Applied and environmental microbiology. 2013; 79(5):1639-45. doi: 10.1128/AEM.03246-12 PMID: 23275516
28. Hargrove TY, Wawrzak Z, Lamb DC, Guengerich FP, Lepesheva GI. Structure-Functional Characterization of Cytochrome P450 Sterol 14alpha-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs. J Biol Chem. 2015; 290(39):23916-34. doi: 10.1074/jbc.M115.677310 PMID: 26269599
29. Parker JE, Warrilow AG, Cools HJ, Martel CM, Nes WD, Fraaije BA, et al. Mechanism of binding of prothioconazole to Mycosphaerella graminicola CYP51 differs from that of other azole antifungals. Applied and environmental microbiology. 2011; 77(4):1460-5. doi: 10.1128/AEM.01332-10 PMID: 21169436
30. Dong F, Li J, Chankvetadze B, Cheng Y, Xu J, Liu X, et al. Chiral triazole fungicide difenoconazole: absolute stereochemistry, stereoselective bioactivity, aquatic toxicity, and environmental behavior in vegetables and soil. Environ Sci Technol. 2013; 47(7):3386-94. doi: 10.1021/es304982m PMID: 23451708
31. Cools HJ, Fraaije BA. Update on mechanisms of azole resistance in Mycosphaerella graminicola and implications for future control. Pest Manag Sci. 2013; 69(2):150-5. doi: 10.1002/ps.3348 PMID: 22730104
32. Sanglard D, Ischer F, Koymans L, Bille J. Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob Agents Chemother. 1998; 42(2):241-53. PMID: 9527767
33. Kakeya H, Miyazaki Y, Miyazaki H, Nyswaner K, Grimberg B, Bennett JE. Genetic analysis of azole resistance in the Darlington strain of Candida albicans. Antimicrob Agents Chemother. 2000; 44 (11):2985-90. PMID: 11036010
34. Fraaije BA, Cools HJ, Kim SH, Motteram J, Clark WS, Lucas JA. A novel substitution I381V in the sterol 14alpha-demethylase (CYP51) of Mycosphaerella graminicola is differentially selected by azole fungicides. Mol Plant Pathol. 2007; 8(3):245-54. doi: 10.1111/j.1364-3703.2007.00388.x PMID: 20507496
35. Leroux P, Albertini C, Gautier A, Gredt M, Walker AS. Mutations in the CYP51 gene correlated with changes in sensitivity to sterol 14 alpha-demethylation inhibitors in field isolates of Mycosphaerella graminicola. Pest Manag Sci. 2007; 63(7):688-98. doi: 10.1002/ps.1390 PMID: 17511023
36. Stammler G, Carstensen M, Koch AE, Semar M, Strobel D, Schlehuber. Frequency of different CYP51-haplotypes of Mycosphaerella graminicola and their impact on epoxiconazole-sensitivity and-field efficacy. Crop Protection. 2008; 27(11):1448-56.
37. Faria-Ramos I, Tavares PR, Farinha S, Neves-Maia J, Miranda IM, Silva RM, et al. Environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in Candida glabrata. FEMS yeast research. 2014; 14(7):1119-23. doi: 10.1111/1567-1364.12193 PMID: 25132632
38. Snelders E, Camps SM, Karawajczyk A, Schaftenaar G, Kema GH, van der Lee HA, et al. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One. 2012; 7 (3):e31801. doi: 10.1371/journal.pone.0031801 PMID: 22396740
39. Battye TG, Kontogiannis L, Johnson O, Powell HR, Leslie AG. iMOSFLM: A new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):271-81. doi: 10.1107/S0907444910048675 PMID: 21460445
40. Evans P. Scaling and assessment of data quality. Acta Crystallogr D Biol Crystallogr. 2006; 62(Pt 1):72-82. Epub 2005/12/22. doi: 10.1107/S0907444905036693 PMID: 16369096
41. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. Journal of applied crystallography. 2007; 40(Pt 4):658-74. Epub 2007/08/01. doi: 10.1107/S0021889807021206 PMID: 19461840
42. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, et al. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):213-21. doi: 10.1107/S0907444909052925 PMID: 20124702
43. Emsley P, Lohkamp B, Scott WG, Cowtan K. Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. Epub 2010/04/13. doi: 10.1107/S0907444910007493 PMID: 20383002
44. Warrilow AG, Melo N, Martel CM, Parker JE, Nes WD, Kelly SL, et al. Expression, purification, and characterization of Aspergillus fumigatus sterol 14-alpha demethylase (CYP51) isoenzymes A and B. Antimicrob Agents Chemother. 2010; 54(10):4225-34. doi: 10.1128/AAC.00316-10 PMID: 20660663
45. Guengerich FP, Martin MV, Sohl CD, Cheng Q. Measurement of cytochrome P450 and NADPH-cytochrome P450 reductase. Nat Protoc. 2009; 4(9):1245-51. doi: 10.1038/nprot.2009.121 PMID: 19661994