Ability of Tetrahydrobiopterin Analogues to Support Catalysis by Inducible Nitric Oxide Synthase: Formation of a Pterin Radical is Required for Enzyme Activity

Biochemistry

Volumn 42, Issue 45, 2003, Pages 13287-13303

  Hurshman, Amy R ^a,d   Krebs, Carsten ^b,e   Edmondson, Dale E ^f   Marletta, Michael A ^a,c  

^a UNIVERSITY OF MICHIGAN   (United States)

^b EMORY UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d SCRIPPS RESEARCH INSTITUTE   (United States)

^e PENNSYLVANIA STATE UNIVERSITY   (United States)

^f EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; CATALYST SUPPORTS; ENZYME KINETICS; HYDROXYLATION; MOLECULAR STRUCTURE; NITROGEN OXIDES; OXIDATION;

ELECTRON STRUCTURE;

BIOCHEMISTRY;

ARGININE; CITRULLINE; HEME; NITRIC OXIDE SYNTHASE; ORNITHINE; PTERIN; TETRAHYDROBIOPTERIN;

ARTICLE; CATALYSIS; ELECTRON TRANSPORT; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME STRUCTURE; HYDROXYLATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FOLDING;

AMINO ACIDS; ARGININE; BINDING SITES; BIOPTERIN; CATALYSIS; DITHIONITE; ELECTRON SPIN RESONANCE SPECTROSCOPY; ENZYME ACTIVATION; FREE RADICALS; FREEZING; HEME; NITRATES; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE II; NITRITES; OXYHEMOGLOBINS; PROTEIN STRUCTURE, TERTIARY; PTERINS; RECOMBINANT PROTEINS; TIME FACTORS;

EID: 0242416195     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi035491p     Document Type: Article

References (68)

1. Marletta, M. A., Hurshman, A. R., and Rusche, K. M. (1998) Catalysis by nitric oxide synthase. Curr. Opin. Chem. Biol. 2, 656-663.
2. Stuehr, D. J., and Ghosh, S. (2000) Enzymology of nitric oxide synthases, Handbook Exp. Pharmacol. 143, 33-70.
3. Alderton, W. K., Cooper, C. E., and Knowles, R. G. (2001) Nitric oxide synthases: structure, function, and inhibition, Biochem. J. 357, 593-615.
4. Stuehr, D. J., Kwon, N. S., Nathan, C. F., Griffith, O. W., Feldman, P. L., and Wiseman, J. (1991) Nω-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine, J. Biol. Chem. 266, 6259-6263.
5. Pufahl, R. A., Nanjappan, P. G., Woodard, R. W., and Marletta, M. A. (1992) Mechanistic probes of N-hydroxylation of L-arginine by the inducible nitric oxide synthase from murine macrophages, Biochemistry 31, 6822-6828.
6. White, K. A., and Marletta, M. A. (1992) Nitric oxide synthase is a cytochrome P-450-type hemoprotein. Biochemistry 31, 6627-6631.
7. Stuehr, D. J., and Ikeda-Saito, M. (1992) Spectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical, J. Biol. Chem. 267, 20547-20550.
8. McMillan, K., Bredt, D. S., Hirsch, D. J., Snyder, S. H., Clark, J. E., and Masters, B. S. (1992) Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide, Proc. Natl. Acad. Sci. U.S.A. 89, 11141-11145.
9. Hevel, J. M., White, K. A., and Marletta, M. A. (1991) Purification of the inducible murine macrophage nitric oxide synthase. Identification as a flavoprotein. J. Biol. Chem. 266, 22789-22791.
10. Stuehr, D. J., Cho, H. J., Kwon, N. S., Weise, M. F., and Nathan, C. F. (1991) Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein, Proc. Natl. Acad. Sci. U.S.A. 88, 7773-7777.
11. Mayer, B., John, M., Heinzel, B., Werner, E. R., Wachter, H., Schultz, G., and Böhme, E. (1991) Brain nitric oxide synthase is a biopterin- and flavin-containing multi-functional oxido-reductase, FEBS Lett. 288, 187-191.
12. Hevel, J. M., and Marletta, M. A. (1992) Macrophage nitric oxide synthase: relationship between enzyme-bound tetrahydrobiopterin and synthase activity, Biochemistry 31, 7160-7165.
13. 2+/calmodulin-independent diaphorase and reductase activities, Biochemistry 31, 3243-3255.
14. Sheta, E. A., McMillan, K., and Masters, B. S. (1994) Evidence fox a bidomain structure of constitutive cerebellar nitric oxide synthase, J. Biol. Chem. 269, 15147-15153.
15. Crane, B. R., Arvai, A. S., Ghosh, D. K., Wu, C., Getzoff, E. D., Stuehr, D. J., and Tainer, J. A. (1998) Structure of nitric oxide synthase oxygenase dimer with pterin and substrate. Science 279, 2121-2126.
16. Raman, C. S., Li, H., Martasek, P., Kral, V., Masters, B. S., and Poulos, T. L. (1998) Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center, Cell 95, 939-950.
17. Hurshman, A. R., Krebs, C., Edmondson, D. E., Huynh, B. H., and Marletta, M. A. (1999) Formation of a pterin radical in the reaction of the heme domain of inducible nitric oxide synthase with oxygen. Biochemistry 38, 15689-15696.
18. Boggs, S., Huang, L., and Stuehr, D. J. (2000) Formation and reactions of the heme-dioxygen intermediate in the first and second steps of nitric oxide synthesis as studied by stopped-flow spectroscopy under single-turnover conditions, Biochemistry 39, 2332-2339.
19. Hurshman, A. R., and Marletta, M. A. (2002) Reactions catalyzed by the heme domain of inducible nitric oxide synthase: Evidence for the involvement of tetrahydrobiopterin in electron transfer, Biochemistry 41, 3439-3456.
20. G-hydroxy-L-arginine by nitric oxide synthase: Evidence for the involvement of the heme in catalysis. Biochem. Biophys. Res. Commun. 193, 963-970.
21. G-hydroxy-L-arginine by nitric oxide synthase, Biochemistry 34, 1930-1941.
22. G-hydroxy-L-arginine and hydrogen peroxide by neuronal nitric oxide synthase: implications for mechanism, Biochemistry 36, 14465-14473.
23. G-hydroxy-L-arginine bound to holo-neuronal nitric oxide synthase, Biochemistry 38, 3704-3710.
24. ω -hydroxy-L-arginine complex of inducible nitric oxide synthase oxygenase dimer with active and inactive pterins, Biochemistry 39, 4608-4621.
25. Rusche, K. M., Spiering, M. M., and Marletta, M. A. (1998) Reactions catalyzed by tetrahydrobiopterin-free nitric oxide synthase, Biochemistry 37, 15503-15512.
26. Adak, S., Wang, Q., and Stuehr, D. J. (2000) Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase. Implications for mechanism, J. Biol. Chem. 275, 33554-33561.
27. Baek, K. J., Thiel, B. A., Lucas, S., and Stuehr, D. J. (1993) Macrophage nitric oxide synthase subunits. Purification, characterization, and role of prosthetic groups and substrate in regulating their association into a dimeric enzyme, J. Biol. Chem. 268, 21120-21129.
28. Abu-Soud, H. M., Loftus, M., and Stuehr, D. J. (1995) Subunit dissociation and unfolding of macrophage NO synthase: relationship between enzyme structure, prosthetic group binding, and catalytic function, Biochemistry 34, 11167-11175.
29. Klatt, P., Schmidt, K., Lehner, D., Glatter, O., Bachinger, H. P., and Mayer, B. (1995) Structural analysis of porcine brain nitric oxide synthase reveals a role for tetrahydrobiopterin and L-arginine in the formation of an SDS-resistant dimer, EMBO J. 14, 3687-3695.
30. Klatt, P., Schmid, M., Leopold, E., Schmidt, K., Werner, E. R., and Mayer, B. (1994) The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain, J. Biol. Chem. 269, 13861-13866.
31. White, K. A. (1994) Studies of the heme environment and electron flow in the inducible murine macrophage nitric oxide synthase, Ph.D. Thesis, The University of Michigan, Ann Arbor, MI.
32. Rodriguez-Crespo, I., Gerber, N. C., and Ortiz de Montellano, P. R. (1996) Endothelial nitric-oxide synthase. Expression in Escherichia coli, spectroscopic characterization, and role of tetrahydrobiopterin in dimer formation, J. Biol. Chem. 271, 11462-11467.
33. Presta, A., Weber-Main, A. M., Stankovich, M. T., and Stuehr, D. J. (1998) Comparative effects of substrates and pterin cofactor on the heme midpoint potential in inducible and neuronal nitric oxide synthases. J. Am. Chem. Soc. 120, 9460-9465.
34. Rusche, K. M., and Marletta, M. A. (2001) Reconstitution of pterin-free inducible nitric-oxide synthase, J. Biol. Chem. 276, 421-427.
35. Bec, N., Gorren, A. C., Voelker, C., Mayer, B., and Lange, R. (1998) Reaction of neuronal nitric-oxide synthase with oxygen at low temperature. Evidence for reductive activation of the oxyferrous complex by tetrahydrobiopterin, J. Biol. Chem. 273, 13502-13508.
36. Bec, N., Gorren, A. C., Mayer, B., Schmidt, P. P., Andersson, K. K., and Lange, R. (2000) The role of tetrahydrobiopterin in the activation of oxygen by nitric-oxide synthase. J. Inorg. Biochem. 81, 207-211.
37. Wei, C. C., Wang, Z. Q., Wang, Q., Meade, A. L., Hemann, C., Hille, R., and Stuehr, D. J. (2001) Rapid kinetic studies link tetrahydrobiopterin radical formation to heme-dioxy reduction and arginine hydroxylation in inducible nitric-oxide synthase, J. Biol. Chem. 276, 315-319.
38. Schmidt, P. P., Lange, R., Gorren, A. C., Werner, E. R., Mayer, B., and Andersson, K. K. (2001) Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy, J. Biol. Inorg. Chem. 6, 151-158.
39. Du, M., Yeh, H. C., Berka, V., Wang, L. H., and Tsai, A. L. (2003) Redox properties of human endothelial nitric-oxide synthase oxygenase and reductase domains purified from yeast expression system, J. Biol. Chem. 278, 6002-6011.
40. Wang, Z. Q., Wei, C. C., Ghosh, S., Meade, A. L., Hemann, C., Hille, R., and Stuehr, D. J. (2001) A conserved tryptophan in nitric oxide synthase regulates heme-dioxy reduction by tetrahydrobiopterin, Biochemistry 40, 12819-12825.
41. Wei, C. C., Wang, Z. Q., Arvai, A. S., Hemann, C., Hille, R., Getzoff, E. D., and Stuehr, D. J. (2003) Structure of tetrahydrobiopterin tunes its electron transfer to the heme-dioxy intermediate in nitric oxide synthase, Biochemistry 42, 1969-1977.
42. Presta, A., Siddhanta, U., Wu, C., Sennequier, N., Huang, L., AbuSoud, H. M., Erzurum, S., and Stuehr, D. J. (1998) Comparative functioning of dihydro- and tetrahydropterins in supporting electron transfer, catalysis, and subunit dimerization in inducible nitric oxide synthase, Biochemistry 37, 298-310.
43. Werner, E. R., Pitters, E., Schmidt, K., Wachter, H., Werner-Felmayer, G., and Mayer, B. (1996) Identification of the 4-amino analogue of tetrahydrobiopterin as a dihydropteridine reductase inhibitor and a potent pteridine antagonist of rat neuronal nitric oxide synthase, Biochem. J. 320, 193-196.
44. Pfeiffer, S., Gorren, A. C., Pitters, E., Schmidt, K., Werner, E. R., and Mayer, B. (1997) Allosteric modulation of rat brain nitric oxide synthase by the pterin-site enzyme inhibitor 4-aminotetrahydrobiopterin, Biochem. J. 328, 349-352.
45. Mayer, B., Wu, C., Gorren, A. C., Pfeiffer, S., Schmidt, K., Clark, P., Stuehr, D. J., and Werner, E. R. (1997) Tetrahydrobiopterin binding to macrophage inducible nitric oxide synthase: heme spin shift and dimer stabilization by the potent pterin antagonist 4-amino-tetrahydrobiopterin, Biochemistry 36, 8422-8427.
46. Riethmuller, C., Gorren, A. C., Pitters, E., Hemmens, B., Habisch, H. J., Heales, S. J., Schmidt, K., Werner, E. R., and Mayer, B. (1999) Activation of neuronal nitric-oxide synthase by the 5-methyl analog of tetrahydrobiopterin. Functional evidence against reductive oxygen activation by the pterin cofactor, J. Biol. Chem. 274, 16047-16051.
47. Werner, E. R., Habisch, H. J., Gorren, A. C., Schmidt, K., Canevari, L., Werner-Felmayer, G., and Mayer, B. (2000) Contrasting effects of N5-substituted tetrahydrobiopterin derivatives on phenylalanine hydroxylase, dihydropteridine reductase, and nitric oxide synthase, Biochem. J. 348, 579-583.
48. Battino, R. (1981) IUPAC Solubility Data Series, Permagon Press, Oxford, UK.
49. Hevel, J. M., and Marletta, M. A. (1994) Nitric-oxide synthase assays, Methods Enzymol. 233, 250-258.
50. Rusche, K. M. (1998) Studies of the nitric oxide synthase catalytic and structural requirement for 6(R)-tetrahydro-L-biopterin, Ph.D. Thesis, The University of Michigan, Ann Arbor, MI.
51. White, R. E., and Coon, M. J. (1982) Heme ligand replacement reactions of cytochrome P-450. Characterization of the bonding atom of the axial ligand trans to thiolate as oxygen, J. Biol. Chem. 257, 3073-3083.
52. Ghosh, D. K., Abu-Soud, H. M., and Stuehr, D. J. (1996) Domains of macrophage NO synthase have divergent roles in forming and stabilizing the active dimeric enzyme. Biochemistry 35, 1444-1449.
53. Gorren, A. C., List, B. M., Schrammel, A., Pitters, E., Hemmens, B., Werner, E. R., Schmidt, K., and Mayer, B. (1996) Tetrahydrobiopterin-free neuronal nitric oxide synthase: Evidence for two identical highly anticooperative pteridine binding sites, Biochemistry 35, 16735-16745.
54. Gorren, A. C., Schrammel, A., Schmidt, K., and Mayer, B. (1997) Thiols and neuronal nitric oxide synthase: Complex formation, competitive inhibition, and enzyme stabilization, Biochemistry 36, 4360-4366.
55. Ehrenberg, A., Hemmerich, P., Müller, F., Okada, T., and Viscontini, M. (1967) Über Pterinchemie. 18. Monohydro- und Trihydropterin-Radikale, Helv. Chim. Acta 50, 411-416.
56. Bobst, A. (1968) Über Pterinchemie. 24. Charakterisierung des 5,6,7,8-Tetrahydropterin-(THP)-Radikals in saurer Lösung, Helv. Chim. Acta 51, 607-613.
57. Gorren, A. C., Kungl, A. J., Schmidt, K., Werner, E. R., and Mayer, B. (2001) Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase, Nitric Oxide 5, 176-186.
58. Abu-Soud, H. M., Gachhui, R., Raushel, F. M., and Stuehr, D. J. (1997) The ferrous-dioxy complex of neuronal nitric oxide synthase. Divergent effects of L-arginine and tetrahydrobiopterin on its stability. J. Biol. Chem. 272, 17349-17353.
59. Sato, H., Sagami, I., Daff, S., and Shimizu, T. (1998) Autoxidation rates of neuronal nitric oxide synthase: Effects of the substrates, inhibitors, and modulators, Biochem. Biophys. Res. Commun. 253, 845-849.
60. 2, J. Biol. Chem. 256, 9457-9465.
61. 5, J. Biol. Chem. 259, 15377-15385.
62. Sennequier, N., Boucher, J. L., Battioni, P., and Mansuy, D. (1995) Superoxide anion efficiently performs the oxidative cleavage of C=NOH bonds of amidoximes and N-hydroxyguanidines with formation of nitrogen-oxides, Tetrahedron Lett. 36, 6059-6062.
63. Mansuy, D., Boucher, J. L., and Clement, B. (1995) On the mechanism of nitric oxide formation upon oxidative cleavage of C=N(OH) bonds by NO synthases and cytochromes P450, Biochimie 77, 661-667.
64. Jousserandot, A., Boucher, J. L., Henry, Y., Niklaus, B., Clement, B., and Mansuy, D. (1998) Microsomal cytochrome-P450-dependent oxidation of N-hydroxyguanidines, amidoximes, and ketoximes: mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides, Biochemistry 37, 17179-17191.
65. ω-hydroxyarginine analogues and various N-hydroxyguanidines by NO synthase II: key role of tetrahydrobiopterin in the reaction mechanism and substrate selectivity, Chem. Res. Toxicol. 14, 202-210.
66. Mansuy, D., and Boucher, J. L. (2002) Oxidation of N-hydroxyguanidines by cytochromes P450 and NO synthases and formation of nitric oxide, Drug Metab. Rev. 34, 593-606.
67. Gorren, A. C., Bec, N., Schrammel, A., Werner, E. R., Lange, R., and Mayer, B. (2000) Low-temperature optical absorption spectra suggest a redox role for tetrahydrobiopterin in both steps of nitric oxide synthase catalysis, Biochemistry 39, 11763-11770.
68. Wang, Z. Q., Wei, C. C., and Stuehr, D. J. (2002) A conserved tryptophan 457 modulates the kinetics and extent of N-hydroxy-L-arginine oxidation by inducible nitric-oxide synthase, J. Biol. Chem. 277, 12830-12837.