Impeded electron transfer from a pathogenic FMN domain mutant of methionine synthase reductase and its responsiveness to flavin supplementation

Biochemistry

Volumn 47, Issue 47, 2008, Pages 12515-12522

  Gherasim, Carmen G ^a   Zaman, Uzma ^a,b   Raza, Ashraf ^a   Banerjee, Ruma ^a,c  

^a UNIVERSITY OF NEBRASKA LINCOLN   (United States)

^b UNIVERSITY OF KARACHI   (Pakistan)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACIDS; AMIDES; AMINES; ANIMAL CELL CULTURE; ATOMS; BIOCHEMISTRY; DEUTERIUM; ELECTRONS; HYDROGEN;

ACIDIC RESIDUES; BINDING DOMAINS; BIO-CHEMICALS; COENZYME SPECIFICITIES; CYTOCHROME C; DEUTERIUM EXCHANGES; DICHLOROINDOPHENOL; DO-MAINS; ELECTRON ACCEPTORS; ELECTRON TRANSFERS; ELEVATED LEVELS; EXCHANGE RATES; GENETIC DISORDERS; HOMOCYSTEINE; METHIONINE METABOLISMS; METHIONINE SYNTHASE; MOLECULAR BASES; OXIDOREDUCTASE; OXIDOREDUCTASES; WILD TYPES;

ENZYMES;

2,6 DICHLOROPHENOLINDOPHENOL; ALANINE; AMIDE; CYTOCHROME C; FERRICYANIDE; FLAVINE MONONUCLEOTIDE; MENADIONE; METHIONINE SYNTHASE; METHIONINE SYNTHASE REDUCTASE; MUTANT PROTEIN; OXIDOREDUCTASE; QUERCETIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RIBOFLAVIN; THREONINE;

AMINO ACID SUBSTITUTION; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BINDING SITE; CONTROLLED STUDY; DEUTERIUM HYDROGEN EXCHANGE; ELECTRON TRANSPORT; ENZYME ACTIVITY; ENZYME REACTIVATION; ENZYME RECONSTITUTION; ENZYME SPECIFICITY; GENE MUTATION; GENE STRUCTURE; HUMAN; MASS SPECTROMETRY; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DEPLETION; PROTEIN DOMAIN; TRANSPORT KINETICS; WILD TYPE;

5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE S-METHYLTRANSFERASE; AMINO ACID SEQUENCE; ANIMALS; CYTOCHROMES C; DEUTERIUM EXCHANGE MEASUREMENT; DIETARY SUPPLEMENTS; ELECTRON TRANSPORT; ENZYME ACTIVATION; FERREDOXIN-NADP REDUCTASE; FLAVIN MONONUCLEOTIDE; FLAVINS; HOMOCYSTINURIA; HUMANS; KINETICS; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; MUTATION; NADH, NADPH OXIDOREDUCTASES; NADP; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; RIBOFLAVIN; SWINE;

EID: 56749112337     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi8008328     Document Type: Article

References (42)

1. Mills, J. L., McPartlin, J. M., Kirke, P. N., Lee, Y. J., Conley, M. R., Weir, D. G., and Scott, J. M. (1995) Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 345, 149-151.
2. Clarke, R., Smith, A. D., Jobst, K. A., Refsum, H., Sutton, L., and Ueland, P. M. (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55, 1449-1455.
3. Refsum, H., Ueland, P. M., Nygard, O., and Vollset, S. E. (1998) Homocysteine and Cardiovascular Disease. Annu. Rev. Med. 49, 31-62.
4. Rosenblatt, D. S. (2001) Inborn errors of folate and cobalamin metabolism, Cambridge University Press, Cambridge.
5. Finkelstein, J. D. (2006) Inborn errors of sulfur-containing amino acid metabolism. J. Nutr. 136, 1750S-1754S.
6. Matthews, R. G. (2001) Cobalamin-dependent methyltransferases. Acc. Chem. Res. 34.
7. Banerjee, R. V., and Matthews, R. G. (1990) Cobalamin-dependent methionine synthase. FASEB J. 4, 1450-1459.
8. Drummond, J., Huang, S., Blumenthal, R. M., and Matthews, R. G. (1993) Assignment of enzymatic function to specific protein regions of cobalamin-dependent methionine synthase from Escherichia coli. Biochemistry 32, 9290-9295.
9. Leclerc, D., Wilson, A., Dumas, R., Gafuik, G, Song, D., Watkins, D., Heng, H H. Q., Rommens, J. M., Scherer, S. W., Rosenblatt, D. S., and Gravel, R. A. (1998) Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Proc. Natl. Acad. Sci. U.S.A. 95, 3059-3064.
10. Olteanu, H., and Banerjee, R. (2001) Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. J. Biol. Chem. 276, 35558-35563.
11. Yamada, K., Gravel, R. A., Toraya, T., and Matthews, R. G. (2006) Human methionine synthase reductase is a molecular chaperone for human methionine synthase. Proc. Natl. Acad. Sci. U.S.A. 103, 9476-9481.
12. Elmore, C. L., Wu, X., Leclerc, D., Watson, E. D., Bottiglieri, T., Krupenko, N. I., Krupenko, S. A., Cross, J. C., Rozen, R., Gravel, R. A., and Matthews, R. G. (2007) Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol. Genet. Metab. 91, 85-97.
13. Porter, T. D., and Kasper, C. B. (1986) NADPH-cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins. Biochemistry 25, 1682-1687.
14. Vermilion, J. L., Ballou, D. P., Massey, V., and Coon, M. J. (1981) Separate roles for FMN and FAD in catalysis by liver microsomal NADPH-cytochrome P-450 reductase. J. Biol. Chem. 256, 266-277.
15. Vermilion, J. L., and Coon, M. J. (1978) Identification of the high and low potential flavins of liver microsomal NADPH-cytochrome P-450 reductase. J. Biol. Chem. 253, 8812-8819.
16. Shen, A. L., Porter, T. D., Wilson, T. E., and Kasper, C. B. (1989) Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis. J. Biol. Chem. 264, 7584-7589.
17. Wolthers, K. R., Basran, J., Munro, A. W., and Scrutton, N. S. (2003) Molecular dissection of human methionine synthase reductase: determination of the flavin redox potentials in full-length enzyme and isolated flavin-binding domains. Biochemistry 42, 3911-3920.
18. Wolthers, K. R., and Scrutton, N. S. (2004) Electron transfer in human methionine synthase reductase studied by stopped-flow spectrophotometry. Biochemistry 43, 490-500.
19. Wang, M., Roberts, D. L., Paschke, R., Shea, T. M., Masters, B. S., and Kim, J. J. (1997) Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc. Natl. Acad. Sci. U.S.A. 94, 8411-8416.
20. Shen, A. L., and Kasper, C. B. (1995) Role of acidic residues in the interaction of NADPH-cytochrome P450 oxidoreductase with cytochrome P450 and cytochrome c. J. Biol. Chem. 270, 27475-27480.
21. Adak, S., Ghosh, S., Abu-Soud, H. M., and Stuehr, D. J. (1999) Role of reductase domain cluster 1 acidic residues in neuronal nitric-oxide synthase. Characterization of the FMN-free enzyme. J. Biol. Chem. 274, 22313-22320.
22. Jenkins, C. M., Genzor, C. G., Fillat, M. F., Waterman, M. R., and Gomez-Moreno, C. (1997) Negatively charged anabaena fiavodoxin residues (Asp144 and Glu145) are important for reconstitution of cytochrome P450 17alpha-hydroxylase activity. J. Biol. Chem. 272, 22509-22513.
23. Wilson, A., Leclerc, D., Rosenblatt, D. S., and Gravel, R. A. (1999) Molecular basis for methionine synthase reductase deficiency in patients belonging to the cb1E complementation group of disorders in folate/cobalamin metabolism. Hum. Mol. Genet. 8 2009-2016.
24. Vilaseca, M. A., Vilarinho, L., Zavadakova, P., Vela, E., Cleto, E., Pineda, M., Coimbra, E., Suormala, T., Fowler, B., and Kozich, V. (2003) Cb1E type of homocystinuria: mild clinical phenotype in two patients homozygous for a novel mutation in the MTRR gene. J. Inherit. Metab. Dis. 26, 361-369.
25. Rosenblatt, D. S., and Cooper, B. A. (1987) Inherited disorders of vitamin B12 metabolism. Blood Rev. 1, 177-182.
26. Muller, P., Horneff, G., and Hennermann, J. B. (2007) [A rare inborn error of intracellular processing of cobalamine presenting with microcephalus and megaloblastic anemia: a report of 3 children]. Klin. Padiatr. 219, 361-367.
27. Olteanu, H., Munson, T., and Banerjee, R. (2002) Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry 41, 13378-13385.
28. Sen, S., Yu, J., Yamanishi, M., Schellhorn, D., and Banerjee, R. (2005) Mapping Peptides Correlated with Transmission of Intrasteric Inhibition and Allosteric Activation in Human Cystathionine β-Synthase. Biochemistry 44, 14210-14216.
29. Olteanu, H., Wolthers, K. R., Munro, A. W., Scrutton, N. S., and Banerjee, R. (2004) Kinetic and thermodynamic characterization of the common polymorphic variants of human methionine synthase reductase. Biochemistry 43, 1988-1997.
30. Knight, K., and Scrutton, N. S. (2002) Stopped-flow kinetic studies of electron transfer in the reductase domain of neuronal nitric oxide synthase: re-evaluation of the kinetic mechanism reveals new enzyme intermediates and variation with cytochrome P450 reductase. Biochem. J. 367, 19-30.
31. Klein, M. L., and Fulco, A. J. (1993) Critical residues involved in FMN binding and catalytic activity in cytochrome P450BM-3. J. Biol. Chem. 268, 7553-7561.
32. Gulati, S., Chen, Z., Brody, L. C., Rosenblatt, D. S., and Banerjee, R. (1997) Defects in auxiliary redox proteins lead to functional methionine synthase deficiency. J. Biol. Chem. 272, 19171-19175.
33. Zhang, J., Martasek, P., Paschke, R., Shea, T., Siler Masters, B. S., and Kim, J. J. (2001) Crystal structure of the FAD/NADPH-binding domain of rat neuronal nitric-oxide synthase. Comparisons with NADPH-cytochrome P450 oxidoreductase. J. Biol. Chem. 276, 37506-37513.
34. Zhao, Q., Modi, S., Smith, G., Paine, M., McDonagh, P. D., Wolf, C. R., Tew, D., Lian, L. Y., Roberts, G. C., and Driessen, H. P. (1999) Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. Protein Sci. 8, 298-306.
35. Sevrioukova, I. F., Li, H., Zhang, H., Peterson, J. A., and Poulos, T. L. (1999) Structure of a cytochrome P450-redox partner electrontransfer complex. Proc. Natl. Acad. Sci. U.S.A. 96, 1863-1868.
36. Wolthers, K. R., Lou, X., Toogood, H. S., Leys, D., and Scrutton, N. S. (2007) Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. Biochemistry 46, 11833-11844.
37. Mudd, S. H., Skovby, F., Levy, H. L., Pettigrew, K. D., Wilcken, B., Pyeritz, R. E., Andria, G., Boers, G. H., Bromberg, I. L., Cerone, R., et al. (1985) The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am. J. Hum. Genet. 37, 1-31.
38. Ames, B. N., Elson-Schwab, I., and Silver, E. A. (2002) High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am. J. Clin. Nutr. 75, 616-658.
39. Kim, Y. J., and Rosenberg, L. E. (1974) On the mechanism of pyridoxine responsive homocystinuria. II. Properties of normal and mutant cystathionine beta-synthase from cultured fibroblasts. Proc. Natl. Acad. Sci. U.S.A. 71, 4821-4825.
40. Aw, T. Y., Jones, D. P., and McCormick, D. B. (1983) Uptake of riboflavin by isolated rat liver cells. J. Nutr. 113, 1249-1254.
41. Rosenblatt, D. S., Thomas, I. T., Watkins, D., Cooper, B. A., and Erbe, R. W. (1987) Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. Am. J. Med. Genet. 26, 377-383.
42. Ogier de Baulny, H., Gerard, M., Saudubray, J. M., and Zittoun, J. (1998) Remethylation defects: guidelines for clinical diagnosis and treatment. Eur. J. Pediatr. 157 (2), S77-83.