Mechanism of flavin reduction in the class 1A dihydroorotate dehydrogenase from Lactococcus lactis

Biochemistry

Volumn 46, Issue 13, 2007, Pages 4028-4036

  Fagan, Rebecca L ^a   Jensen, Kaj Frank ^b   Björnberg, Olof ^b,c   Palfey, Bruce A ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c LUND UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL BONDS; IONIZATION; OXIDATION; PH EFFECTS; PROTEINS; REDUCTION;

DIHYDROOROTATE (DHO); FLAVIN REDUCTION; FMN PROSTHETIC GROUP; LACTOCOCCUS LACTIS;

ENZYME KINETICS;

DIHYDROOROTATE DEHYDROGENASE; QUERCETIN;

ARTICLE; BINDING AFFINITY; ENZYME ACTIVE SITE; ENZYME MECHANISM; ENZYME SUBSTRATE COMPLEX; HYDROGEN BOND; LACTOCOCCUS LACTIS; NONHUMAN; OXIDATION REDUCTION REACTION; PH; PKA; PRIORITY JOURNAL; REDUCTION; STRUCTURE ACTIVITY RELATION;

AMINO ACID SUBSTITUTION; BINDING SITES; CYSTEINE; FLAVIN MONONUCLEOTIDE; HYDROGEN-ION CONCENTRATION; LACTOCOCCUS LACTIS; OXIDATION-REDUCTION; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS;

LACTOCOCCUS LACTIS;

EID: 34047235161     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi602460n     Document Type: Article

References (25)

1. Björnberg, O., Rowland, P., Larsen, S., and Jensen, K. F. (1997) Active site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis, Biochemistry 36, 16197-16205.
2. Jones, M. E. (1980) Pyrimidine nucleotide biosynthesis in animals: Genes, enzymes, and regulation of ump biosynthesis, Annu. Rev. Biochem. 49, 253-279.
3. Nagy, M., Lacroute, F., and Thomas, D. (1992) Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts, Proc. Natl. Acad. Sci. U.S.A. 89, 8966-8970.
4. Nielsen, F. S., Andersen, P. S., and Jensen, K. F. (1996) The B form of dihydroorotate dehydrogenase from Lactococcus lactis consists of two different subunits, encoded by the pyrDB and pyrK genes, and contains FMN, FAD, and [FeS] redox centers, J. Biol. Chem. 271, 29359-29365.
5. Annoura, T., Nara, T., Makiuchi, T., Hashimoto, T., and Aoki, T. (2005) The origin of dihydroorotate dehydrogenase genes of kinetoplastids, with special reference to their biological significance and adaptation to anaerobic, parasitic conditions, J. Mol. Evol. 60, 113-127.
6. Palfey, B. A., Björnberg, O., and Jensen, K. F. (2001) Specific inhibition of a family 1A dihydroorotate dehydrogenase by benzoate pyrimidine analogues, J. Med. Chem. 44, 2861-2864.
7. Rowland, P., Björnberg, O., Nielsen, F. S., Jensen, K. F., and Larsen, S. (1998) The crystal structure of Lactococcus lactis dihydroorotate dehydrogenase A complexed with the enzyme reaction product throws light on its enzymatic function, Protein Sci. 7, 1269-1279.
8. Nørager, S., Jensen, K. F., Björnberg, O., and Larsen, S. (2002) E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenases, Structure 10, 1211-1223.
9. Liu, S., Neidhardt, E. A., Grossman, T. H., Ocain, T., and Clardy, J. (2000) Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents, Structure 8, 25-33.
10. Blattmann, P., and Retey, J. (1972) Stereospecificity of the dihydroorotate-dehydrogenase reaction, Eur. J. Biochem. 30, 130-137.
11. Fagan, R. L., Nelson, M. N., Pagano, P. M., and Palfey, B. A. (2006) Mechanism of flavin reduction in class 2 dihydroorotate dehydrogenases, Biochemistry 45, 14926-14932.
12. Nielsen, F. S., Rowland, P., Larsen, S., and Jensen, K. F. (1996) Purification and characterization of dihydroorotate dehydrogenase A from Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of the enzyme, Protein Sci. 5, 852-856.
13. Pascal, R. A., Jr., and Walsh, C. T. (1984) Mechanistic studies with deuterated dihydroorotates on the dihydroorotate oxidase from Crithidia fasciculata, Biochemistry 23, 2745-2752.
14. Palfey, B. A. (2003) Time resolved spectral analysis, in Kinetic analysis of macromolecules (Johnson, K. A., Ed.) pp 203-227, Oxford University Press, New York.
15. Williams, C. H., Jr., Arscott, L. D., Matthews, R. G., Thorpe, C., and Wilkinson, K. D. (1979) Methodology employed for anaerobic spectrophotometric titrations and for computer-assisted data analysis, Methods Enzymol. 62, 185-198.
16. Palfey, B. A., Björnberg, O., and Jensen, K. F. (2001) Insight into the chemistry of flavin reduction and oxidation in Escherichia coli dihydroorotate dehydrogenase obtained by rapid reaction studies, Biochemistry 40, 4381-4390.
17. Shi, J., Dertouzos, J., Gafni, A., Steel, D., and Palfey, B. A. (2006) Single-molecule, kinetics reveals signatures of half-sites reactivity in dihydroorotate dehydrogenase A catalysis, Proc. Natl. Acad. Sci. U.S.A. 103, 5775-5780.
18. Nørager, S., Arent, S., Björnberg, O., Ottosen, M., Lo Leggio, L., Jensen, K. F., and Larsen, S. (2003) Lactococcus lactis dihydroorotate dehydrogenase A mutants reveal important facets of the enzymatic function, J. Biol. Chem. 278, 28812-28822.
19. Ottosen, M. B., Björnberg, O., Nørager, S., Larsen, S., Palfey, B. A., and Jensen, K. F. (2002) The dimeric dihydroorotate dehydrogenase A from Lactococcus lactis dissociates reversibly into inactive monomers, Protein Sci. 11, 2575-2583.
20. Massey, V. (1990) in Flavins and Flavoproteins (Curti, B., Ronchi, S., and Zanetti, G., Eds.) pp 59-66, Walter de Gruyter, Berlin.
21. Björnberg, O., Jordan, D. B., Palfey, B. A., and Jensen, K. F. (2001) Dihydrooxonate is a substrate of dihydroorotate dehydrogenase (DHOD) providing evidence for involvement of cysteine and serine residues in base catalysis, Arch. Biochem. Biophys. 391, 286-294.
22. Palfey, B. A., and Massey, V. (1998) Flavin-dependent enzymes, in Comprehensive biological catalysis, volume iii: Radical reactions and oxidation/reduction (Sinnott, N., Ed.) pp 83-154, Academic Press, New York.
23. Bruice, T. C., Fife, T. H., Bruno, J. J., and Brandon, N. E. (1962) Hydroxyl group catalysis. II. The reactivity of the hydroxyl group of serine. The nucleophilicity of alcohols and the ease of hydrolysis of their acetyl esters as related to their pKa, Biochemistry 1, 7-12.
24. Bigelisen, J. (1955) Statistical mechanics of isotope systems with small quantum corrections. I. General considerations and the rule of the geometric mean, J. Chem. Phys. 23, 2264-2267.
25. Cleland, W. W. (1980) Measurement of Isotope Effects by the Equilibrium Perturbation Technique, Methods Enzymol. 64, 104-125.