Disruption of the proton relay network in the class 2 dihydroorotate dehydrogenase from Escherichia coli

Biochemistry

Volumn 48, Issue 41, 2009, Pages 9801-9809

  Kow, Rebecca L ^a,c   Whicher, Jonathan R ^b   McDonald, Claudia A ^a   Palfey, Bruce A ^a,b   Fagan, Rebecca L ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE SITE; DE NOVO SYNTHESIS; E. COLI; HYDROGEN BOND NETWORKS; ORDERS OF MAGNITUDE; RELAY NETWORK; SITE DIRECTED MUTAGENESIS; WATER MOLECULE;

AMINO ACIDS; BINDING SITES; CATALYSTS; CRYSTAL ATOMIC STRUCTURE; ENZYMES; ESCHERICHIA COLI; HYDROGEN; PROTONS;

HYDROGEN BONDS;

DIHYDROOROTATE DEHYDROGENASE; PHENYLALANINE; PROTON; QUERCETIN; THREONINE;

ARTICLE; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME METABOLISM; ENZYME PURIFICATION; ENZYME STRUCTURE; ESCHERICHIA COLI; HYDROGEN BOND; HYDROPHOBICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTON TRANSPORT; SITE DIRECTED MUTAGENESIS; SYNTHESIS;

CATALYTIC DOMAIN; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; FLAVIN MONONUCLEOTIDE; GENE EXPRESSION REGULATION, BACTERIAL; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HYDROGEN BONDING; HYDROGEN-ION CONCENTRATION; KINETICS; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; OXIDATION-REDUCTION; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PROTEIN CONFORMATION;

ESCHERICHIA COLI;

EID: 70350045277     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi901024m     Document Type: Article

References (33)

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. (Pubitemid 28065034)
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. Baumgartner, R., Walloschek, M., Kralik, M., Gotschlich, A., Tasler, S., Mies, J., and Leban, J. (2006) Dual binding mode of a novel series of DHODH inhibitors. J. Med. Chem. 49, 1239-1247.
6. Hansen, M., Le Nours, J., Johansson, E., Antal, T., Ullrich, A., Loffler, M., and Larsen, S. (2004) Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 13, 1031-1042. (Pubitemid 38429225)
7. Hurt, D. E., Widom, J., and Clardy, J. (2006) Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor. Acta Crystallogr. D62, 312-323. (Pubitemid 44185140)
8. 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. (Pubitemid 30051339)
9. 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. (Pubitemid 35254010)
10. Walse, B., Dufe, V. T., Svensson, B., Fritzson, I., Dahlberg, L., Khairoullina, A., Wellmar, U., and Al-Karadaghi, S. (2008) The structures of human dihydroorotate dehydrogenase with and without inhibitor reveal conformational flexibility in the inhibitor and substrate binding sites. Biochemistry 47, 8929-8936.
11. 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. (Pubitemid 32319583)
12. 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.
13. Small, Y. A., Guallar, V., Soudackov, A. V., and Hammes-Schiffer, S. (2006) Hydrogen bonding pathways in human dihydroorotate dehydrogenase. J. Phys. Chem. B 110, 19704-19710.
14. Björnberg, O., Gruner, 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 38, 2899-2908. (Pubitemid 129501344)
15. Palfey, B. A. (2003) Time Resolved Spectral Analysis. In Kinetic Analysis of Macromolecules (Johnson, K. A., Ed.) pp 203-227, Oxford Unversity Press, New York.
16. 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.
17. Massey, V. (1990) A simple method for the determination of redox potentials. In Flavins and Flavoproteins (Curti, B., Ronchi, S., and Zanetti, G., Eds.) pp 59-66, Walter de Gruyter, Berlin.
18. 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. 377, 178-186.
19. Noerager, 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.
20. Wolfe, A. E., Thymark, M., Gattis, S. G., Fagan, R. L., Hu, Y. C., Johansson, E., Arent, S., Larsen, S., and Palfey, B. A. (2007) Interaction of benzoate pyrimidine analogues with class 1A dihydroorotate dehydrogenase from Lactococcus lactis. Biochemistry 46, 5741-5753. (Pubitemid 46764123)
21. Zameitat, E., Pierik, A. J., Zocher, K., and Loffler, M. (2007) Dihydroorotate dehydrogenase from Saccharomyces cerevisiae: Spectroscopic investigations with the recombinant enzyme throw light on catalytic properties and metabolism of fumarate analogues. FEMS Yeast Res. 7, 897-904. (Pubitemid 47256377)
22. Fagan, R. L., and Palfey, B. A. (2009) Roles in Binding and Chemistry for Conserved Active Site Residues in the Class 2 Dihydroorotate Dehydrogenase from Escherichia coli. Biochemistry 48, 7169-7178.
23. Fagan, R. L., Jensen, K. F., Bj̈ornberg, O., and Palfey, B. A. (2007) Mechanism of flavin reduction in the class 1A dihydroorotate dehydrogenase from Lactococcus lactis. Biochemistry 46, 4028-4036. (Pubitemid 46536066)
24. Arakaki, T. L., Buckner, F. S., Gillespie, J. R., Malmquist, N. A., Phillips, M. A., Kalyuzhniy, O., Luft, J. R., Detitta, G. T., Verlinde, C. L., Van Voorhis, W. C., Hol, W. G., and Merritt, E. A. (2008) Characterization of Trypanosoma brucei dihydroorotate dehydrogenase as a possible drug target: Structural, kinetic and RNAi studies. Mol. Microbiol. 68, 37-50.
25. Inaoka, D. K., Sakamoto, K., Shimizu, H., Shiba, T., Kurisu, G., Nara, T., Aoki, T., Kita, K., and Harada, S. (2008) Structures of Trypanosoma cruzi dihydroorotate dehydrogenase complexed with substrates and products: Atomic resolution insights into mechanisms of dihydroorotate oxidation and fumarate reduction. Biochemistry 47, 10881-10891.
26. 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. (Pubitemid 28272893)
27. 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. (Pubitemid 32149749)
28. Wolfenden, R., and Radzicka, A. (1994)On the probability of finding a water molecule in a nonpolar cavity. Science 265, 936-937. (Pubitemid 24282718)
29. Voth, G. A. (2006) Computer simulation of proton solvation and transport in aqueous and biomolecular systems. Acc. Chem. Res. 39, 143-150.
30. LeBrun, L. A., Park, D. H., Ramaswamy, S., and Plapp, B. V. (2004) Participation of histidine-51 in catalysis by horse liver alcohol dehydrogenase. Biochemistry 43, 3014-3026. (Pubitemid 38352252)
31. Schlichting, I., Berendzen, J., Chu, K., Stock, A. M., Maves, S. A., Benson, D. E., Sweet, R. M., Ringe, D., Petsko, G. A., and Sligar, S. G. (2000) The catalytic pathway of cytochrome P450cam at atomic resolution. Science 287, 1615-1622. (Pubitemid 30127756)
32. Vidakovic, M., Sligar, S. G., Li, H., and Poulos, T. L. (1998) Understanding the role of the essential Asp251 in cytochrome P450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Biochemistry 37, 9211-9219. (Pubitemid 28307674)
33. Makris, T. M., von Koenig, K., Schlichting, I., and Sligar, S. G. (2007) Alteration of P450 distal pocket solvent leads to impaired proton delivery and changes in heme geometry. Biochemistry 46, 14129-14140. (Pubitemid 350250307)