Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole

PLoS Neglected Tropical Diseases

Volumn 4, Issue 4, 2010, Pages

  Chen, Chiung Kuang ^a   Leung, Siegfried S F ^a   Guilbert, Christophe ^a   Jacobson, Matthew P ^a   Mckerrow, James H ^a   Podust, Larissa M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUCONAZOLE; POSACONAZOLE; STEROL 14ALPHA DEMETHYLASE; ANTIFUNGAL AGENT; CYTOCHROME P450; TRIAZOLE DERIVATIVE;

ANTIFUNGAL RESISTANCE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG BINDING; DRUG EFFICACY; DRUG STRUCTURE; DRUG TARGETING; HYDROPHOBICITY; NONHUMAN; TRYPANOSOMA BRUCEI; TRYPANOSOMA CRUZI; AMINO ACID SEQUENCE; CHEMICAL STRUCTURE; CHEMISTRY; METABOLISM; MOLECULAR GENETICS; PROTEIN BINDING; PROTEIN TERTIARY STRUCTURE; SEQUENCE ALIGNMENT; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANTIFUNGAL AGENTS; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; FLUCONAZOLE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; SEQUENCE ALIGNMENT; TRIAZOLES; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMA CRUZI;

EID: 77952358375     PISSN: None     EISSN: None     Source Type: Journal    
DOI: 10.1371/journal.pntd.0000651     Document Type: Article

References (62)

1. Chagas C (1909) Nova trypanosomiase humana. Gaceta Medica da Bahia 40: 433-440.
2. World Health Organization (2002) Control of Chagas disease: second report of the WHO expert committee. Geneva: WHO.
3. Coura JR, De Castro SL (2002) A Critical Review on Chagas Disease Chemotherapy. Memórias do Instituto Oswaldo Cruz 97: 3-24.
4. McKerrow JH, Doyle PS, Engel JC, Podust LM, Robertson SA, et al. (2009) Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz 104: 263-269.
5. Roberts CW, McLeod R, Rice DW, Ginger M, Chance ML, et al. (2003) Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa. Mol Biochem Parasitol 126: 129-142.
6. Urbina JA, Docampo R (2003) Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 19: 495-501.
7. Buckner F (2008) Sterol 14-demethylase inhibitors for Trypanosoma cruzi infections. In: Majumder HK, ed. Drug Targets in Kinetoplastid Parasites. New York: Springer. pp 61-80.
8. de Souza W, Rodrigues JC (2009) Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs. Interdiscip Perspect Infect Dis 2009. 642502 p.
9. Kauffman CA, Malani AN, Easley C, Kirkpatrick P (2007) Posaconazole. Nat Rev Drug Discov 6: 183-184.
10. Molina J, Martins-Filho O, Brener Z, Romanha AJ, Loebenberg D, et al. (2000) Activities of the triazole derivative SCH 56592 (posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts. Antimicrob Agents Chemother 44: 150-155.
11. Ferraz ML, Gazzinelli RT, Alves RO, Urbina JA, Romanha AJ (2007) The anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole. Antimicrob Agents Chemother 51: 1359-1364.
12. Morris MI (2009) Posaconazole: a new oral antifungal agent with an expanded spectrum of activity. Am J Health Syst Pharm 66: 225-236.
13. Buckner F, Yokoyama K, Lockman J, Aikenhead K, Ohkanda J, et al. (2003) A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents. Proc Natl Acad Sci U S A 100: 15149-15153.
14. Hucke O, Gelb MH, Verlinde CL, Buckner FS (2005) The protein farnesyltransferase inhibitor Tipifarnib as a new lead for the development of drugs against Chagas disease. J Med Chem 48: 5415-5418.
15. Suryadevara PK, Olepu S, Lockman JW, Ohkanda J, Karimi M, et al. (2009) Structurally simple inhibitors of lanosterol 14alpha-demethylase are efficacious in a rodent model of acute Chagas disease. J Med Chem 52: 3703-3715.
16. Chen C-K, Doyle PS, Yermalitskaya LV, Mackey ZB, Ang KKH, et al. (2009) Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit. PLoS Negl Trop Dis 3: e372.
17. Chennamaneni NK, Arif J, Buckner FS, Gelb MH (2009) Isoquinoline-based analogs of the cancer drug clinical candidate tipifarnib as anti-Trypanosoma cruzi agents. Bioorg Med Chem Lett 19: 6582-6584.
18. Podust LM, Poulos TL, Waterman MR (2001) Crystal structure of cytochrome P450 14alpha-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc Natl Acad Sci USA 98: 3068-3073.
19. Podust LM, Yermalitskaya LV, Lepesheva GI, Podust VN, Dalmasso EA, et al. (2004) Estriol bound and ligand-free structures of sterol 14alpha-demethylase. Structure 12: 1937-1945.
20. Nasser Eddine A, von Kries JP, Podust MV, Warrier T, Kaufmann SH, et al. (2008) X-ray structure of 4,49-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase CYP51). J Biol Chem 283: 15152-15159.
21. Lepesheva GI, Zaitseva NG, Nes WD, Zhou W, Arase M, et al. (2006) CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix defines substrate preferences of sterol 14alpha-demethylase. J Biol Chem 281: 3577-3585.
22. Marichal P, Koymans L, Willemsens S, Bellens D, Verhasselt P, et al. (1999) Contribution of mutations in the cytochrome P450 14alpha-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Microbiology 145: 2701-2713.
23. Sanglard D, Ischer F, Koymans L, Bille J (1998) Amino acid substitutions in the cytochrome P450 lanosterol 14alpha-demethylase (CYP51) from azole-resistant Candida albicans clinical isolates contributing to the resistance to azole antifungal agents. Antimicrob Agents Chemother 42: 241-253.
24. Asai K, Tsuchimori N, Okonogi K, Perfect JR, Gotoh O, et al. (1999) Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450. Antimicrob Agents Chemother 43: 1163-1169.
25. Kelly SL, Lamb DC, Kelly DE (1999) Y132H substitution in Candida albicans sterol 14alpha-demethylase confers fluconazole resistance by preventing binding to haem. FEMS Microbiol Lett 180: 171-175.
26. Perea S, Lopez-Ribot JL, Kirkpatrick WR, McAtee RK, Santillan RA, et al. (2001) Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 45: 2676-2684.
27. Kudo M, Ohi M, Aoyama Y, Nitahara Y, Chung SK, et al. (2005) Effects of Y132H and F145L substitutions on the activity, azole resistance and spectral properties of Candida albicans sterol 14-demethylase P450 (CYP51): a live example showing the selection of altered P450 through interaction with environmental compounds. J Biochem (Tokyo) 137: 625-632.
28. Wheat LJ, Connolly P, Smedema M, Durkin M, Brizendine E, et al. (2006) Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who failed fluconazole. J Antimicrob Chemother 57: 1235-1239.
29. Chau AS, Chen G, McNicholas PM, Mann PA (2006) Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae. Antimicrob Agents Chemother 50: 3917-3919.
30. El-Sayed NM, Myler PJ, Blandin G, Berriman M, Crabtree J, et al. (2005) Comparative genomics of trypanosomatid parasitic protozoa. Science 309: 404-409.
31. Coppens I, Courtoy PJ (2000) The adaptative mechanisms of Trypanosoma brucei for sterol homeostasis in its different life-cycle environments. Annu Rev Microbiol 54: 129-156.
32. Barnes HJ, Arlotto MP, Waterman MR (1991) Expression and enzymatic activity of recombinant cytochrome P450 17 alpha-hydroxylase in Escherichia coli. Proc Natl Acad Sci U S A 88: 5597-5601.
33. Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J Biol Chem 239: 2379-2385.
34. Holton J, Alber T (2004) Automated protein crystal structure determination using ELVES. Proc Natl Acad Sci U S A 101: 1537-1542.
35. Cowtan K (2006) The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr D Biol Crystallogr 62: 1002-1011.
36. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60: 2126-2132.
37. Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53: 240-255.
38. Winn MD, Isupov MN, Murshudov GN (2001) Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr D Biol Crystallogr 57: 122-133.
39. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, et al. (2004) Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47: 1739-1749.
40. Zhu K, Shirts MR, Friesner RA, Jacobson MP (2007) Multiscale optimization of a truncated Newton minimization algorithm and application to proteins and protein-ligand complexes. J Chem Theory Comput 3: 640-648.
41. Podust LM, Stojan J, Poulos TL, Waterman MR (2001) Substrate recognition sites in 14alpha-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. J Inorg Biochem 87: 227-235.
42. Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, et al. (2009) Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15: 1068-1076.
43. Li X, Brown N, Chau AS, Lopez-Ribot JL, Ruesga MT, et al. (2004) Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. J Antimicrob Chemother 53: 74-80.
44. Mann PA, Parmegiani RM, Wei SQ, Mendrick CA, Li X, et al. (2003) Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14alpha-demethylase. Antimicrob Agents Chemother 47: 577-581
45. Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela JL (2003) A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 47: 1120-1124.
46. Nascimento AM, Goldman GH, Park S, Marras SA, Delmas G, et al. (2003) Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob Agents Chemother 47: 1719-1726.
47. da Silva Ferreira ME, Capellaro JL, dos Reis Marques E, Malavazi I, Perlin D, et al. (2004) In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob Agents Chemother 48: 4405-4413.
48. Chen J, Li H, Li R, Bu D, Wan Z (2005) Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J Antimicrob Chemother 55: 31-37.
49. Xiao L, Madison V, Chau AS, Loebenberg D, Palermo RE, et al. (2004) Three-dimensional models of wild-type and mutated forms of cytochrome P450 14alpha-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding. Antimicrob Agents Chemother 48: 568-574.
50. Buckner FS, Wilson AJ, White TC, Van Voorhis WC (1998) Induction of resistance to azole drugs in Trypanosoma cruzi. Antimicrob Agents Chemother 42: 3245-3250.
51. Pinto e Silva AT, Costa-de-Oliveira S, Silva-Dias A, Pina-Vaz C, Rodrigues AG (2009) Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azoles. FEMS Yeast Res 9: 626-633.
52. Pfaller MA, Diekema DJ, Ghannoum MA, Rex JH, Alexander BD, et al. (2009) Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods. J Clin Microbiol 47: 3142-3146.
53. Chau AS, Mendrick CA, Sabatelli FJ, Loebenberg D, McNicholas PM (2004) Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob Agents Chemother 48: 2124-2131.
54. Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela JL (2004) Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob Agents Chemother 48: 2747-2750.
55. Rodriguez-Tudela JL, Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Monzon A, et al. (2008) Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus. Antimicrob Agents Chemother 52: 2468-2472.
56. Antoine JC, Prina E, Jouanne C, Bongrand P (1990) Parasitophorous vacuoles of Leishmania amazonensis-infected macrophages maintain an acidic pH. Infect Immun 58: 779-787.
57. Antoine J-C, Prina E, Lang T, Courret N (1998) The biogenesis and properties of the parasitophorous vacuoles that harbour Leishmania in murine macrophages. Trends in Microbiology 6: 392-401.
58. DeLano WL (2002) The PyMOL molecular graphics system. San Carlos, CA, USA: DeLano Scientific.
59. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14: 33-38.
60. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
61. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673-4680.
62. Gouet P, Courcelle E, Stuart DI, Metoz F (1999) ESPript: multiple sequence alignments in PostScript. Bioinformatics 15: 305-308. 63. Maestro. New York, NY, USA: Schrodinger, LLC.