Biochemical characterization of recombinant dihydroorotate dehydrogenase from the opportunistic pathogenic yeast Candida albicans

FEBS Journal

Volumn 273, Issue 14, 2006, Pages 3183-3191

  Zameitat, Elke ^a   Gojković, Zoran ^b,c   Knecht, Wolfgang ^b,d   Piškur, Jure ^b,e   Löffler, Monika ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^c ASTRAZENECA R AND D   (Sweden)

^d ZGene AS   (Denmark)

^e LUND UNIVERSITY   (Sweden)

Author keywords

Antimycotics; Candida albicans; Dihydroorotate dehydrogenase; Pyrimidines; Redoxal

Indexed keywords

2 (3,3 DICHLOROALLYL) 3 HYDROXY 1,4 NAPHTHOQUINONE; ACETYLSALICYLIC ACID; ALLOXAN; ALPHA RESORCYLIC ACID; AMOBARBITAL; ANTIFUNGAL AGENT; ANTIMYCIN A1; ATOVAQUONE; BIPHENYL DERIVATIVE; BREQUINAR; CARBOXIN; CARBOXYLIC ACID DERIVATIVE; CIPROFLOXACIN; CLINDAMYCIN; DIANISIDINE; DIHYDROOROTATE DEHYDROGENASE; DIHYDROOROTATE DEHYDROGENASE INHIBITOR; ECTOSIN; FLUCYTOSINE; FLUOROOROTIC ACID; FLUOROURACIL; LAWSONE; LICOCHALCONE A; MENADIONE; NCI 73735; PROTOCATECHUIC ACID; PYRIMIDINE NUCLEOTIDE; RECOMBINANT ENZYME; REDOXAL; TERIFLUNOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SEQUENCE; ANTIFUNGAL ACTIVITY; ARTICLE; CANDIDA ALBICANS; CONTROLLED STUDY; DRUG TARGETING; ENZYME ACTIVITY; ENZYME KINETICS; ENZYME SPECIFICITY; ESCHERICHIA COLI; MOLECULAR CLONING; NONHUMAN; NUCLEOTIDE SEQUENCE; OPPORTUNISTIC INFECTION; POLYACRYLAMIDE GEL ELECTROPHORESIS; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PYRIMIDINE SYNTHESIS; WESTERN BLOTTING;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; AMINOBIPHENYL COMPOUNDS; BIPHENYL COMPOUNDS; CANDIDA ALBICANS; CONSERVED SEQUENCE; ENZYME INHIBITORS; ESCHERICHIA COLI; GLUTATHIONE TRANSFERASE; HUMANS; HYDROGEN-ION CONCENTRATION; INHIBITORY CONCENTRATION 50; KINETICS; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MUTATION; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PROTEIN STRUCTURE, TERTIARY; RECOMBINANT FUSION PROTEINS; SEQUENCE HOMOLOGY, AMINO ACID; SUBSTRATE SPECIFICITY;

CANDIDA ALBICANS; ESCHERICHIA COLI; MAMMALIA;

EID: 33745623955     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2006.05327.x     Document Type: Article

References (38)

1. Whiteway M & Oberholzer U (2003) Candida morphogenesis and host-pathogen interactions. Curr Microbiol 7, 350-357.
2. Löffler J & Stevens DA (2003) Antifungal drug resistance. Clin Infect Dis 36, 31-41.
3. Sanglar D & Odds FC (2002) Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2, 73-85.
4. Prasad R & Kapoor K (2005) Multidrug resistance in yeast Candida. Int Rev Cytol 242, 215-248.
5. Hope WW, Taberno L, Denning DW & Anderson MJ (2004) Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob Agents Chemother 48, 4377-4386.
6. Löffler M, Fairbanks L, Zameitat E, Marinaki T & Simmonds HA (2005) Pyrimidine pathways in health and disease. Trends Mol Med 11, 430-437.
7. Rao TVG, Verme RS & Prasad R (1983) Transport of purine, pyrimidine bases and nucleosides in Candida albicans, a pathogenic yeast. Biochem Int 6, 409-417.
8. Knecht W & Löffler M (1998) Species-related inhibition of human and rat dihydroorotate dehydrogenase by immunosuppressive isoxazol and cinchoninic acid derivatives. Biochem Pharmacol 56, 1259-1264.
9. Christopherson RI, Lyons SD & Wilson PK (2002) Inhibitors of de novo nucleotide biosynthesis as drugs. Acc Chem Res 35, 961-971.
10. Jones ME (1980) Pyrimidine nucleotide biosynthesis in animals: gene, enzymes and regulation of UMP biosynthesis. Annu Rev Biochem 49, 253-279.
11. Nara T, Hshimoto T & Aoki T (2000) Evolutionary implications of the mosaic pyrimidine-bio synthetic pathway in eurkayotes. Gene 257, 209-222.
12. Rawls J, Knecht W, Diekert K, Lill R & Löffler M (2000) Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase. Eur J Biochem 267, 2079-2087.
13. Blattmann P & Retey J (1972) Stereospecificity of the dihydroorotate-dehydrogenase reaction. Eur J Biochem 30, 130-137.
14. Mohsen AA, Rigby SEJ, Jensen KF, Munro AW & Scrutton NS (2004) Thermodynamic basis of electron transfer in dihydroorotate dehydrogenase B from Lactococcus lactis: analysis by potentiometry, EPR spectroscopy and ENDOR spectroscopy. Biochemistry 43, 6498-6510.
15. Nagy M, Lacroute F & Thomas D (1992) Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeast. Proc Natl Acad Sci USA 89, 8966-8970.
16. Gojković Z, Knecht W, Zameitat E, Warneboldt J, Coutelis JB, Pynyaha Y, Neuveglise C, Møller K, Loffler M & Piškur J (2004) Horizontal gene transfer promoted evolution of the ability to propagate under anaerobic conditions in yeasts. Mol Genet Genomics 271, 387-393.
17. Zameitat E, Knecht W, Piškur J & Löffler M (2004) Two different dihydroorotate dehydrogenases from yeast Saccharomyces kluyveri. FEBS Lett 568, 129-134.
18. Knecht W, Bergjohann U, Gonski S, Kirschbaum B & Löffler M (1996) Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression system, and kinetic investigation of the purified recombinant enzyme. Eur J Biochem 240, 292-301.
19. Santos MAS, Keith G & Tuite MF (1993) Non-standard translational events in Candida abicans mediated by an unusual seryl-tRNA with a 5́-CAG-3́ (leucine) anticodon. EMBO J 12, 607-617.
20. Bader B, Knecht W, Fries M & Löffler M (1998) Expression, purification, and characterization of histidine-tagged rat and human flavoenzyme dihydroorotate dehydrogenase. Protein Expr Purif 13, 414-422.
21. Haberkorn A (1996) Chemotherapy of human and animal coccidiosis: state and perspectives. Parasitol Res 82, 193-199.
22. Olliaro P & Wirth D (1997) New targets for antimalarial drug discovery. J Pharm Pharmacol 49, 29-33.
23. Liu S, Neidhardt EA, Grossman TH, Ocain T & Clardy J (2000) Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents. Structure 8, 25-33.
24. Schatz G & Dobberstein B (1996) Common principles of protein translocation across membranes. Science 271, 1519-1526.
25. Truscott KN, Brandner K & Pfanner N (2003) Mechanisms of protein import into mitochondria. Curr Biol 13, R326-R337.
26. Ullrich A, Knecht W, Fries M & Löffler M (2001) Recombinant expression of N-terminal truncated mutants of the membrane bound mouse, rat and human flavoenzyme dihydroorotate dehydrogenase. A versatile tool to rate inhibitor effects? Eur J Biochem 268, 1861-1868.
27. Nørager S, Jensen KF, Björnberg O & Larsen S (2002) E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenase. Structure 10, 1211-1223.
28. Joseph-Horne T, Hollomon DW & Wood PM (2001) Fungal respiration: a fusion of standard and alternative components. Biochim Biophys Acta 1504, 179-195.
29. Tsai AL, Olsen JS & Palmer G (1987) The kinetics of reoxidation of yeast complex III. J Biol Chem 262, 8677-8684.
30. Helmerhorst EJ, Murphy MP, Troxler RF & Oppenheim FG (2002) Characterization of the mitochondrial respiratory pathways in Candida albicans. Biochim Biophys Acta 1556, 73-80.
31. Herrmann M, Schleyerbach R & Kirschbaum BJ (2000) Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 47, 273-289.
32. Hansen M, LeNours J, Johansson E, Antal T, Ullrich A, Löffler M & Larsen S (2004) Inhibitior binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci 13, 1031-1042.
33. Knecht W, Henseling J & Löffler M (2000) Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid. Chem Biol Interact 124, 61-76.
34. Knecht W & Löffler M (2000) Redoxal as a new lead structure for dihydroorotate dehydrogenase inhibitors: a kinetic study of the inhibition mechanism. FEBS Lett 467, 27-30.
35. Löffler M, Klein A, Hayek-Ouassini M, Knecht W & Konrad L (2004) Dihydroorotate dehydrogenase mRNA and protein expression analysis in normal and drug-resistant cells. Nucleosides, Nucleotides, Nucleic Acids 23, 1281-1285.
36. Chen M, Christensen SB, Blom J, Lemmich E, Nadelmann L, Fich K, Theander TG & Kharazmi A (1993) Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob Agents Chemother 37, 2550-2556.
37. Tournaire C, Caujolle R, Payard M, Commenges G, Bessières MH, Bories C, Loiseau P & Gayral P (1996) Synthesis and protozoocidal activities of quinones. Eur J Med Chem 31, 507-511.
38. Dietz C, Hinsch E & Löffler M (2000) Immunocytochemical detection of mitochondrial dihydroorotate dehydrogenase in human spermatozoa. Int J Androl 23, 294-299.