Mechanism of inducible nitric-oxide synthase dimerization inhibition by novel pyrimidine imidazoles

Journal of Biological Chemistry

Volumn 288, Issue 27, 2013, Pages 19685-19697

  Nagpal, Latika ^a   Haque, Mohammad M ^b   Saha, Amit ^c   Mukherjee, Nirmalya ^c   Ghosh, Arnab ^b   Ranu, Brindaban C ^c   Stuehr, Dennis J ^b   Panda, Koustubh ^a  

^a UNIVERSITY OF CALCUTTA   (India)

^b LERNER RESEARCH INSTITUTE   (United States)

^c DEPARTMENT OF MATERIALS SCIENCE   (India)

Author keywords

[No Author keywords available]

Indexed keywords

CELLULAR TOXICITIES; INDUCIBLE NITRIC OXIDE SYNTHASE (INOS); NITRIC-OXIDE SYNTHASE; OVER-EXPRESSION; SPECTROPHOTOMETRIC ANALYSIS; STOPPED-FLOW KINETICS; TETRAHYDROBIOPTERIN; THERAPEUTIC CONTROL;

AMINO ACIDS; AROMATIC COMPOUNDS; DIMERS; DISEASE CONTROL; MONOMERS; NITRIC OXIDE; PLANTS (BOTANY); PROPORTIONAL CONTROL SYSTEMS;

DIMERIZATION;

2 [1 [2 (IMIDAZOL 1 YL)PYRIMIDIN 4 YL]PIPERAZIN 2 YL] N [[BENZO(D)(1,3) DIOXOL 6 YL]METHYL]ACETAMIDE; [[(BENZO(D)(1,3)DIOXOL 6 YL)METHYLCARBAMOYL]METHYL] 4 [2 (IMIDAZOL 1 YL)PYRIMIDIN 4 YL]PIPERAZINE 1 CARBOXYLIC ACID; ARGININE; IMIDAZOLE DERIVATIVE; INDUCIBLE NITRIC OXIDE SYNTHASE; TETRAHYDROBIOPTERIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING KINETICS; CONTROLLED STUDY; DIMERIZATION; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; ENZYME SYNTHESIS; FLOW KINETICS; GEL FILTRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SPECTROPHOTOMETRY;

DIMERIZATION INHIBITORS; ENZYME INHIBITORS; ENZYME KINETICS; NITRIC OXIDE; NITRIC-OXIDE SYNTHASE; NITROSATIVE STRESS; PYRIMIDINE IMIDAZOLES;

AMINO ACID SUBSTITUTION; ANIMALS; ARGININE; BIOPTERIN; CELL LINE; ENZYME INHIBITORS; HEME; IMIDAZOLES; MICE; MUTATION, MISSENSE; NITRIC OXIDE SYNTHASE TYPE II; PROTEIN MULTIMERIZATION; PYRIMIDINES;

EID: 84880057432     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.446542     Document Type: Article

References (45)

1. Daff, S. (2010) NO synthase: structures and mechanisms. Nitric Oxide 23, 1-11
2. Li, H., and Poulos, T. L. (2005) Structure-function studies on nitric oxide synthases. J. Inorg. Biochem. 99, 293-305
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. Bredt, D. S., Hwang, P. M., and Snyder, S. H. (1990) Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347, 768-770
5. Nakane, M., Schmidt, H. H., Pollock, J. S., Förstermann, U., and Murad, F. (1993) Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett. 316, 175-180
6. Martin, W., Furchgott, R. F., Villani, G. M., and Jothianandan, D. (1986) Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor. J. Pharmacol. Exp. Ther. 237, 529-538
7. O'Dell, T. J., Huang, P. L., Dawson, T. M., Dinerman, J. L., Snyder, S. H., Kandel, E. R., and Fishman, M. C. (1994) Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science 265, 542-546
8. Cho, H. J., Xie, Q. W., Calaycay, J., Mumford, R. A., Swiderek, K. M., Lee, T. D., and Nathan, C. (1992) Calmodulin is a subunit of nitric oxide synthase from macrophages. J. Exp. Med. 176, 599-604
9. Michel, T., and Feron, O. (1997) Nitric oxide synthases: which, where, how, and why? J. Clin. Invest. 100, 2146-2152
10. Schmidt, H. H., and Walter, U. (1994) NO at work. Cell 78, 919-925
11. Stuehr, D. J. (1999) Mammalian nitric oxide synthases. Biochim. Biophys. Acta 1411, 217-230
12. 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
13. Klatt, P., Pfeiffer, S., List, B. M., Lehner, D., Glatter, O., Bächinger, H. P., Werner, E. R., Schmidt, K., and Mayer, B. (1996) Characterization of heme-deficient neuronal nitric-oxide synthase reveals a role for heme in subunit dimerization and binding of the amino acid substrate and tetrahydrobiopterin. J. Biol. Chem. 271, 7336-7342
14. Rodríguez-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
15. Panda, K., Ghosh, S., and Stuehr, D. J. (2001) Calmodulin activates intersubunit electron transfer in the neuronal nitric-oxide synthase dimer. J. Biol. Chem. 276, 23349-23356
16. Ichinose, F., Hataishi, R., Wu, J. C., Kawai, N., Rodrigues, A. C., Mallari, C., Post, J. M., Parkinson, J. F., Picard, M. H., Bloch, K. D., and Zapol, W. M. (2003) A selective inducible NOS dimerization inhibitor prevents systemic, cardiac, and pulmonary hemodynamic dysfunction in endotoxemic mice. Am. J. Physiol. Heart Circ. Physiol. 285, H2524-H2530
17. Enkhbaatar, P., Murakami, K., Shimoda, K., Mizutani, A., Traber, L., Phillips, G., Parkinson, J., Salsbury, J. R., Biondo, N., Schmalstieg, F., Burke, A., Cox, R., Hawkins, H., Herndon, D., and Traber, D. (2003) Inducible nitric oxide synthase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury. Am. J. Physiol. Heart Circ. Physiol. 285, H2430-H2436
18. Lincoln, J., Hoyle, C. H., and Burnstock, G. (1997) Nitric Oxide in Health and Diseases. pp. 1-356, Cambridge University Press, Cambridge, UK
19. Stuehr, D. J. (1997) Structure-function aspects in the nitric oxide synthases. Annu. Rev. Pharmacol. Toxicol. 37, 339-359
20. Kröncke, K. D., Fehsel, K., and Kolb-Bachofen, V. (1995) The action ofNO and its role in autoimmune diabetes mellitus. Biol. Chem. Hoppe-Seyler 376, 327-343
21. Milstien, S., Sakai, N., Brew, B. J., Krieger, C., Vickers, J. H., Saito, K., and Heyes, M. P. (1994) Cerebrospinal fluid nitrite/nitrate levels in neurologic diseases. J. Neurochem. 63, 1178-1180
22. Bieńkowska-Haba, M., Liebhart, J., and Cembrzyńska-Nowak, M. (2006) Nitric oxide production by pulmonary leukocytes from induced sputum in patients with asthma and its effect on epithelial cell viability. Arch. Immunol. Ther. Exp. 54, 201-207
23. Radomski, M. W., Palmer, R. M., and Moncada, S. (1990) Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 87, 10043-10047
24. Boullerne, A. I., Petry, K. G., Meynard, M., and Geffard, M. (1995) Indirect evidence for nitric oxide involvement in multiple sclerosis by characterization of circulating antibodies directed against conjugated S-nitrosocysteine. J. Neuroimmunol. 60, 117-124
25. Griffith, O. W., and Stuehr, D. J. (1995) Nitric oxide synthases: properties and catalytic mechanism. Annu. Rev. Physiol. 57, 707-736
26. Sennequier, N., Wolan, D., and Stuehr, D. J. (1999) Antifungal imidazoles block assembly of inducible NO synthase into an active dimer. J. Biol. Chem. 274, 930-938
27. McMillan, K., Adler, M., Auld, D. S., Baldwin, J. J., Blasko, E., Browne, L. J., Chelsky, D., Davey, D., Dolle, R. E., Eagen, K. A., Erickson, S., Feldman, R. I., Glaser, C. B., Mallari, C., Morrissey, M. M., Ohlmeyer, M. H., Pan G, Parkinson, J. F., Phillips, G. B., Polokoff, M. A., Sigal N. H., Vergona, R., Whitlow, M., Young, T. A., and Devlin, J. J. (2000) Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry. Proc. Natl. Acad. Sci. U.S.A. 97, 1506-1511
28. Blasko, E., Glaser, C. B., Devlin, J. J., Xia, W., Feldman, R. I., Polokoff, M. A., Phillips, G. B., Whitlow, M., Auld, D. S., McMillan, K., Ghosh, S., Stuehr, D. J., and Parkinson, J. F. (2002) Mechanistic studies with potent and selective inducible nitric-oxide synthase dimerization inhibitors. J. Biol. Chem. 277, 295-302
29. Gahman, T. C., Herbert, M. R., Lang, H., Thayer, A., Symons, K. T., Nguyen, P. M., Massari, M. E., Dozier, S., Zhang, Y., Sablad, M., Rao, T. S., Noble, S. A., Shiau, A. K., and Hassig, C. A. (2011) Identification and SAR of selective inducible nitric oxide synthase (iNOS) dimerization inhibitors. Bioorg. Med. Chem. Lett. 21, 6888-6894
30. Panda, K., Chawla-Sarkar, M., Santos, C., Koeck, T., Erzurum, S. C., Parkinson, J. F., and Stuehr, D. J. (2005) Visualizing inducible nitric-oxide synthase in living cells with a heme-binding fluorescent inhibitor. Proc. Natl. Acad. Sci. U.S.A. 102, 10117-10122
31. Davey, D. D., Adler, M., Arnaiz, D., Eagen, K., Erickson, S., Guilford, W., Kenrick, M., Morrissey, M. M., Ohlmeyer, M., Pan, G., Paradkar, V. M., Parkinson, J., Polokoff, M., Saionz, K., Santos, C., Subramanyam, B., Vergona, R., Wei, R. G., Whitlow, M., Ye, B., Zhao, Z. S., Devlin, J. J., and Phillips, G. (2007) Design, synthesis, and activity of 2-imidazol-1-ylpyrimidine-derived inducible nitric oxide synthase dimerization inhibitors. J. Med. Chem. 50, 1146-1157
32. Wu, C., Zhang, J., Abu-Soud, H., Ghosh, D. K., and Stuehr, D. J. (1996) High-level expression of mouse inducible nitric oxide synthase in Escherichia coli requires co-expression with calmodulin. Biochem. Biophys. Res. Commun. 222, 439-444
33. Ghosh, D. K., Crane, B. R., Ghosh, S., Wolan, D., Gachhui, R., Crooks, C., Presta, A., Tainer, J. A., Getzoff, E. D., and Stuehr, D. J. (1999) Inducible nitric oxide synthase: role of the N-terminal β-hairpin hook and pterinbinding segment in dimerization and tetrahydrobiopterin interaction. EMBO J. 18, 6260-6270
34. Ghosh, D. K., Wu, C., Pitters, E., Moloney, M., Werner, E. R., Mayer, B., and Stuehr, D. J. (1997) Characterization of the inducible nitric oxide synthase oxygenase domain identifies a 49-amino acid segment required for subunit dimerization and tetrahydrobiopterin interaction. Biochemistry 36, 10609-10619
35. 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
36. Stuehr, D. J., and Marletta, M. A. (1987) Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res. 47, 5590-5594
37. Klatt, P., Schmidt, K., Lehner, D., Glatter, O., Bächinger, 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 SDSresistant dimer. EMBO J. 14, 3687-3695
38. Albakri, Q. A., and Stuehr, D. J. (1996) Intracellular assembly of inducible NO synthase is limited by nitric oxide-mediated changes in heme insertion and availability. J. Biol. Chem. 271, 5414-5421
39. Panda, K., Rosenfeld, R. J., Ghosh, S., Meade, A. L., Getzoff, E. D., and Stuehr, D. J. (2002) Distinct dimer interaction and regulation in nitricoxide synthase types I, II, and III. J. Biol. Chem. 277, 31020-31030
40. 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
41. Pant, K., Bilwes, A. M., Adak, S., Stuehr, D. J., and Crane, B. R. (2002) Structure of a nitric oxide synthase heme protein from Bacillus subtilis. Biochemistry 41, 11071-11079
42. Crane, B. R., Arvai, A. S., Gachhui, R., Wu, C., Ghosh, D. K., Getzoff, E. D., Stuehr, D. J., and Tainer, J. A. (1997) The structure of nitric oxide synthase oxygenase domain and inhibitor complexes. Science 278, 425-431
43. Fedorov, R., Vasan, R., Ghosh, D. K., and Schlichting, I. (2004) Structures of nitric oxide synthase isoforms complexed with the inhibitor ARR17477 suggest a rational basis for specificity and inhibitor design. Proc. Natl. Acad. Sci. U.S.A. 101, 5892-5897
44. Panda, K., Adak, S., Aulak, K. S, Santolini, J., McDonald, J. F, Stuehr, D. J. (2003) Distinct influence of N-terminal elements on neuronal nitric-oxide synthase structure and catalysis. J. Biol. Chem. 278, 37122-37131
45. Rodríguez-Crespo, I., Moënne-Loccoz, P., Loehr, T. M., and Ortiz de Montellano, P. R. (1997) Endothelial nitric oxide synthase: modulations of the distal heme site produced by progressive N-terminal deletions. Biochemistry 36, 8530-8538