S279 point mutations in Candida albicans sterol 14-α demethylase (CYP51) reduce in vitro inhibition by fluconazole

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 4, 2012, Pages 2099-2107

  Warrilow, Andrew G S ^a   Mullins, Jonathan G L ^a   Hull, Claire M ^a   Parker, Josie E ^a   Lamb, David C ^a   Kelly, Diane E ^a   Kelly, Steven L ^a  

^a SWANSEA UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FLUCONAZOLE; HEME; ITRACONAZOLE; LANOSTEROL; OXYGEN; STEROL 14ALPHA DEMETHYLASE; VORICONAZOLE;

ANTIFUNGAL RESISTANCE; ARTICLE; BINDING AFFINITY; CANDIDA ALBICANS; ENZYME ACTIVITY; ENZYME INHIBITION; IC 50; IN VITRO STUDY; MOLECULAR MODEL; MUTANT; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; WILD TYPE;

14-ALPHA DEMETHYLASE INHIBITORS; AMINO ACID SEQUENCE; ANTIFUNGAL AGENTS; AZOLES; BINDING, COMPETITIVE; CANDIDA ALBICANS; DNA, FUNGAL; FLUCONAZOLE; KINETICS; LANOSTEROL; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; POINT MUTATION; POLYMERASE CHAIN REACTION; PROTEIN BINDING; RECOMBINANT PROTEINS; STEROL 14-DEMETHYLASE;

EID: 84858669755     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.05389-11     Document Type: Article

References (53)

1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. 1990. Basic local alignment search tool. J. Mol. Biol. 215:403-410.
2. Alvarez-Rueda N, et al. 2011. Amino acid substitutions at the major insertion loop of Candida albicans sterol 14alpha-demethylase are involved in fluconazole resistance. PLoS One 6:e21239.
3. Arase M, Waterman MR, Kagawa N. 2006. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem. Biophys. Res. Commun. 344:400-405.
4. Bancel F, Bec N, Ebel C, Lange R. 1997. A central role for water in the control of the spin state of cytochrome P-450scc. Eur. J. Biochem. 250: 276-285. (Pubitemid 28012664)
5. Bellamine A, Lepesheva GI, Waterman MR. 2004. Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J. Lipid Res. 45:2000-2007. (Pubitemid 40990894)
6. Bellamine A, Mangla AT, Nes WD, Waterman MR. 1999. Characterisation and catalytic properties of the sterol 14α-demethylase from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 96:8937-8942. (Pubitemid 29374686)
7. Cools HJ, et al. 2010. Heterologous expression of mutated eburicol 14 alpha-demethylase (CYP51) proteins of Mycosphaerella graminicola to assess effects on azole fungicide sensitivity and intrinsic protein function. Appl. Environ. Microbiol. 76:2866-2872.
8. Copeland RA. 2005. Evaluation of enzyme inhibitors in drug discovery: a guide for medicinal chemists and pharmacologists, p 178-213. Wiley-Interscience, New York, NY.
9. Coste A, et al. 2007. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot. Cell 6:1889-1904. (Pubitemid 47585577)
10. Estabrook RW, Peterson JA, Baron J, Hildebrandt AG. 1972. The spectrophotometric measurement of turbid suspensions of cytochromes associated with drug metabolism. Methods Pharmacol. 2:303-350.
11. Eswar N, et al. 2003. Tools for comparative protein structure modeling and analysis. Nucleic Acids Res. 31:3375-3380. (Pubitemid 37442163)
12. Grunberg R, Nilges M, Leckner J. 2007. Biskit - a software platform for structural bioinformatics. Bioinformatics 23:769-770. (Pubitemid 46554731)
13. Hendlich M, Rippmann F, Barnickel G. 1997. LIGSITE: automatic and efficient detection of potential small molecule-binding sites in proteins. J. Mol. Graph. Model. 15:359-363. (Pubitemid 28409807)
14. Jefcoate CR. 1978. Measurement of substrate and inhibitor binding to microsomal cytochrome P-450 by optical-difference spectroscopy. Methods Enzymol. 52:258-279.
15. Jefcoate CR, Gaylor JL, Calabrese RL. 1969. Ligand interactions with cytochrome P450. I. Binding of primary amines. Biochemistry 8:3455-3463.
16. Ji H, et al. 2000. A three-dimensional model of lanosterol 14α-demethylase of Candida albicans and its interaction with azole antifungals. J. Med. Chem. 43:2493-2505. (Pubitemid 30437131)
17. Kakeya H, et al. 2000. Genetic analysis of azole resistance in the Darlington strain of Candida albicans. Antimicrob. Agents Chemother. 44:2985-2990.
18. Kelly SL, Lamb DC, Kelly DE, Loeffler J, Einsele H. 1996. Resistance to fluconazole and amphotericin in Candida albicans from AIDS patients. Lancet 348:1523-1524. (Pubitemid 26400271)
19. Kelly SL, Lamb DC, Jackson CJ, Warrilow AGS, Kelly DE. 2003. The biodiversity of microbial cytochromes P450. Adv. Microb. Physiol. 47: 131-186. (Pubitemid 37214150)
20. Lamb DC, et al. 1999. Characteristics of the heterologously expressed human lanosterol 14α-demethylase (other names: P45014DM, CYP51, P45051) and inhibition of the purified human and Candida albicans CYP51 with azole antifungal agents. Yeast 15:755-763. (Pubitemid 29308798)
21. Lamb DC, Kelly DE, White TC, Kelly SL. 2000. The R467K amino acid substitution in Candida albicans sterol 14α-demethylase causes reduced drug resistance through reduced affinity. Antimicrob. Agents Chemother. 44:63-67. (Pubitemid 30010673)
22. Lepesheva GI, et al. 2010. Crystal structures of Trypanosoma brucei sterol 14α-demethylase and implications for selective treatment of human infections. J. Biol. Chem. 285:1773-1780.
23. Lepesheva GI, Podust LM, Bellamine A, Waterman MR. 2001. Folding requirements are different between sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs. J. Biol. Chem. 276:28413-28420.
24. Lepesheva GI, Virus C, Waterman MR. 2003. Conservation in the CYP51 family: role of the B′ helix/BC loop and helices F and G in enzyme function. Biochemistry 42:9091-9101. (Pubitemid 36935417)
25. Löffler J, et al. 1997. Molecular analysis of cyp51 from fluconazoleresistant Candida albicans strains. FEMS Microbiol. Lett. 151:263-268. (Pubitemid 27293310)
26. Lutz JD, et al. 2009. Expression and functional characterization of cytochrome P450 26A1, a retinoic acid hydroxylase. Biochem. Pharmacol. 77:258 -268.
27. Marichal P, et al. 1999. Contribution of mutations in the cytochrome P450 14α-demethylase (erg11p, cyp51p) to azole resistance in Candida albicans. Microbiology 145:2701-2713. (Pubitemid 29485885)
28. Martel CM, et al. 2010. Identification and characterization of four azoleresistant erg3 mutations of Candida albicans. Antimicrob. Agents Chemother. 54:4527-4533.
29. Morio F, Loge C, Besse B, Hennequin C, Le Pape P. 2010. Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. Diagn. Microbiol. Infect. Dis. 66:373-384.
30. Morrison JF. 1969. Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors. Biochim. Biophys. Acta 185:269 -286.
31. Mullins JGL, et al. 2011. Molecular modelling of the emergence of azole resistance in Mycosphaerella graminicola. PLoS One 6:e20973.
32. Notredame C, Higgins DG, Heringa J. 2000. T-COFFEE: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302:205-217.
33. Omura T, Sato R. 1964. The carbon monoxide-binding pigment of liver microsomes. J. Biol. Chem. 239:2379 -2385.
34. Park H-G, et al. 2011. Heterologous expression and characterization of the sterol 14α-demethylase CYP51F1 from Candida albicans. Arch. Biochem. Biophys. 509:9-15.
35. Pettersen EF, et al. 2004. UCSF Chimera - a visualization system for exploratory research and analysis. J. Comput. Chem. 25:1605-1612.
36. Pfaller MA, Diekema DJ. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20:133-163. (Pubitemid 46167771)
37. Podust LM, Poulos TL, Waterman MR. 2001. Crystal structure of cytochrome P450 14α-demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors. Proc. Natl. Acad. Sci. U. S. A. 98:3068-3073. (Pubitemid 32220800)
38. Podust LM, Stojan J, Poulos TL, Waterman MR. 2001. Substrate recognition sites in 14α-sterol demethylase form comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. J. Inorg. Biochem. 87:227-235. (Pubitemid 34017227)
39. Ravichandran KG, Boddupalli SS, Hasermann CA, Peterson JA, Deisenhofer J. 1993. Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science 261:731-736. (Pubitemid 23278388)
40. Renaud JP, Davydov DR, Heirweigh KPM, Mansuy D, Hui Bon Hoa G. 1996. Thermodynamic studies of substrate binding and spin transitions in human cytochrome P-450 3A4 expressed in yeast microsomes. Biochem. J. 319:675-681. (Pubitemid 26386176)
41. Richardson MD. 2005. Changing patterns and trends in systemic fungal infections. J. Antimicrob. Agents Chemother. 56(Suppl S1):i5-i11.
42. Rupp B, Raub S, Marian C, Höltje HD. 2005. Molecular design of two sterol 14α-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole. J. Comput. Aided Mol. Des. 19:149 -163.
43. Sanglard D, Ischer F, Koymans L, Bille J. 1998. Amino acid substitutions in the P-450 lanosterol 14α-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob. Agents Chemother. 42:241-253. (Pubitemid 28114426)
44. Shyadehi AZ, et al. 1996. The mechanism of the acyl-carbon bond cleavage reaction catalyzed by recombinant sterol 14alpha-demethylase of Candida albicans (other names are: lanosterol 14alpha-demethylase, P-450, and CYP51). J. Biol. Chem. 271:12445-12450.
45. Sims CR, Ostrosky-Zeichner L, Rex JH. 2005. Invasive candidiasis in immunocompromised hospitalized patients. Arch. Med. Res. 36:660-671. (Pubitemid 41436235)
46. Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. 1995. Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. FEMS Microbiol. Lett. 131: 337-341.
47. Venkateswarlu K, Lamb DC, Kelly DE, Manning NJ, Kelly SL. 1998. The N-terminal membrane domain of yeast NADPH-cytochrome P450 (CYP) oxidoreductase is not required for catalytic activity in sterol biosynthesis or in reconstitution of CYP activity. J. Biol. Chem. 273:4492-4496. (Pubitemid 28103189)
48. Warrilow AGS, et al. 2009. Identification, characterization and azole-binding properties of Mycobacterium smegmatis CYP164A2, a homolog of ML2088, the sole cytochrome P450 gene of Mycobacterium leprae. Antimicrob. Agents Chemother. 53:1157-1164.
49. Warrilow AGS, et al. 2010. Azole binding properties of Candida albicans sterol 14-α demethylase (CaCYP51). Antimicrob. Agents Chemother. 54: 4235-4245.
50. Watson PF, Rose ME, Ellis SW, England H, Kelly SL. 1989. Defective sterol C5-6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals. Biochem. Biophys. Res. Commun. 164:1170-1175. (Pubitemid 19283967)
51. Wheeler DL, et al. 2007. Database resources of the National Centre for Biotechnology Information. Nucleic Acids Res. 35:D5-D12. (Pubitemid 46056160)
52. White TC. 1997. The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14α- demethylase in Candida albicans. Antimicrob. Agents Chemother. 41: 1488-1494. (Pubitemid 27289673)
53. Xiao L, et al. 2004. Three-dimensional models of wild-type and mutated forms of cytochrome P450 14α-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding. Antimicrob. Agents Chemother. 48:568-574. (Pubitemid 38141718)