The dimeric dihydroorotate dehydrogenase A from Lactococcus lactis dissociates reversibly into inactive monomers

Protein Science

Volumn 11, Issue 11, 2002, Pages 2575-2583

  Ottosen, Mette Brimheim ^a   Björnberg, Olof ^b   Nørager, Sofie ^c   Larsen, Sine ^a   Palfey, Bruce Allan ^a   Jensen, Kaj Frank ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Dissociation kinetics; Flavin; Nucleotide synthesis; Oligomerization; Oxido reductase; Quaternary structure

Indexed keywords

ALANINE; DIHYDROOROTATE DEHYDROGENASE; DIHYDROOROTATE DEHYDROGENASE A; DIMER; MONOMER; UNCLASSIFIED DRUG; OROTIC ACID; OXIDOREDUCTASE;

ARTICLE; DIMERIZATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME MECHANISM; ENZYME SUBUNIT; LACTOCOCCUS LACTIS; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; CHEMICAL STRUCTURE; CHEMISTRY; ENZYMOLOGY; GENETIC COMPLEMENTATION; GENETICS; METABOLISM; PROTEIN QUATERNARY STRUCTURE;

BACTERIA (MICROORGANISMS); LACTOCOCCUS; LACTOCOCCUS LACTIS; STREPTOCOCCUS;

DIMERIZATION; GENETIC COMPLEMENTATION TEST; LACTOCOCCUS LACTIS; MODELS, MOLECULAR; OROTIC ACID; OXIDOREDUCTASES; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PROTEIN STRUCTURE, QUATERNARY;

EID: 0036839243     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1110/ps.0220302     Document Type: Article

References (30)

1. Argyrou, A. and Washabaugh, M.W. 1999. Proton transfer from the C5-proR/ pros positions of L-dihydroorotate: General-base catalysis, isotope effects, and internal return. J. Am. Chem. Soc. 121: 12054-12062.
2. Argyrou, A., Washabaugh, M.W., and Pickart, C.M. 2000. Dihydroorotate dehydrogenase from Clostridium oroticum is a Class 1B enzyme and utilizes a concerted mechanism of catalysis. Biochemistry 39: 10373-10384.
3. Björnberg, O., Rowland, P., Larsen, S., and Jensen, K.F. 1997. The active site of dihydroorotate dehydrogenase A from Lactococcus lactis investigated by chemical modification and mutagenesis. Biochemistry 36: 16197-16205.
4. Bjömberg, O., Grüner, A.C., Roepstorff, P., and Jensen, K.F. 1999. The activity of Escherichia coli dihydroorotate dehydrogenase is dependent on a conserved loop identified by sequence homology, mutagenesis and limited proteolysis. Biochemistry 28: 2899-2908.
5. Bjömberg, 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.
6. Deuschle, U., Kammerer, W., Gentz, R., and Bujard, H. 1986. Promoters of E. coli. A hierarchy of in vivo strength indicates alternate structures. EMBO J. 5: 2987-2994.
7. Fraaije, M.W. and Mattevi, A. 2000. Flavoenzymes: Diverse catalysts with recurrent features. TIBS 25: 126-132.
8. Gao, G., Nara, T., Nakajima-Shimada, J., and Aoki, T. 1999. Novel organization and sequences of five genes encoding all six enzymes for de novo pyrimidine biosynthesis in Trypanosoma cruzi. J. Mol. Biol. 285: 149-161.
9. Jensen, K.F. and Björnberg, O. 1998. Evolutionary and functional families of dihydroorotate dehydrogenases. Paths to Pyrimidines 6: 20-28.
10. Jiang, W., Locke, G., Harpel, M.R., Copeland, R.A., and Marcinkeviciene, J. 2000. Role of Lys100 in human dihydroorotate dehydrogenase: Mutagenesis studies and chemical rescue by external amines. Biochemistry 39: 7990-7997.
11. Jordan, D.B., Bisaha, J.J., and Picollelli, M.A. 2000. Catalytic properties of dihydroorotate dehydrogenase from Saccharomyces cerevisiae: Studies on pH, alternate substrates, and inhibitors. Arch. Biochem. Biophys. 378: 84-92.
12. Kahler, A.E., Nielsen, F.S., and Switzer, R.L. 1999. Biochemical characterization of the heteromeric Bacillus subtilis dihydroorotate dehydrogenase and its isolated subunits. Arch. Biochem. Biophys. 37: 191-201.
13. Karibian, D. 1978. Dihydroorotate dehydrogenase (Escherichia coli). Methods Enzymol. 51: 58-63.
14. Kraulis, P.J. 1991. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallography 24: 946-950.
15. 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.
16. Marcinkeviciene, J., Tinney, L.M., Wang, K.H., Rogers, M.J., and Copeland, R.A. 1999. Dihydroorotate dehydrogenase B of Enterococcus faecalis. Characterization and insights into chemical mechanism. Biochemistry 38: 13129-13137.
17. Marcinkeviciene, J., Jiang, W., Locke, G., Kopcho, L.M., Rogers, M.J., and Copeland, R.A. 2000. A second dihydroorotate dehydrogenase (Type A) of the human pathogen Enterococcus faecalis: Expression, purification and steady-state kinetic mechanism. Arch. Biochem. Biophys. 277: 178-186.
18. Merritt, E.A. and Bacon, D.J. 1997. Raster3D photorealistic molecular graphics. Methods Enzymol. 277: 505-524.
19. Miller, J.H. 1972. Experiments in molecular genetics, p. 433. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
20. Nagy, M., Lacroute, F., and Thomas, D. 1992. Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts. Proc. Natl. Acad. Sci. 89: 8966-8970.
21. Neet, K.E., and Ainslie, Jr., G.R. 1980. Hysteretic enzymes. Methods Enzymol. 64: 192-226.
22. Nielsen, F.S., Andersen, P.S., and Jensen, K.F. 1996a. 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 centres. J. Biol. Chem. 271: 29359-29365.
23. Nielsen, F.S., Rowland, P., Larsen, S., and Jensen, K.F. 1996b. Purification and characterization of dihydroorotate dehydrogenase A from Lactococcus lactis, crystallization and preliminary X-ray diffraction studies of the enzyme. Protein Sci. 5: 857-861.
24. Nørager, S., Jensen, K.F., Björnberg, O., and Larsen, S. 2002. E. coli dihydroorotate dehydrogenase reveals structural and functional differences between different classes of dihydroorotate dehydrogenases. Structure (in press).
25. 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.
26. Pascal, R.A., Trang, N.L., Cerami, A., and Walsh, C. 1983. Purification and properties of dihydroorotate oxidase from Crithidia fasciculata and Trypanosoma brucei. Biochemistry 22: 171-178.
27. 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 reaction product ortate throws light on its enzymatic function. Protein Sci. 7: 1269-1279.
28. Rowland, P., Larsen, S., Nielsen, F.S., Björnberg, O., and Jensen, K.F. 1997a. Properties of dihydroorotate dehydrogenase A from Lactococcus lactis. Crystallization and three dimensional structure of the enzyme. In Flavins and flavoproteins 1996 (eds. K.J. Stevenson, V.I. Massey, and C.H. Williams, Jr.), pp. 927-930. University of Calgary Press. UBC Press, Vancouver, Canada.
29. Rowland, P., Nielsen, F.S., Jensen, K.F., and Larsen, S. 1997b. The crystal structure of the flavin containing enzyme dihydroorotate dehydrogenase A from Lactococcus lactis. Structure 5: 239-250.
30. Rowland, P., Nørager, S., Jensen. K.F., and Larsen, S. 2000. Structure of dihydroorotate dehydrogenase B: Electron transfer between two flavin groups bridged by an iron-sulphur cluster. Structure 8: 1227-1238.