Arg410 near the heme proximal ligand of neuronal nitric oxide synthase is critical for both substrate recognition and electron transfer

Chemistry Letters

Volumn 33, Issue 6, 2004, Pages 752-753

  Yadav, Jyoti ^a   Fujiwara, Shigeyoshi ^a   Sagami, Ikuko ^a   Shimizu, Toru ^a  

^a TOHOKU UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; HEME; NITRIC OXIDE SYNTHASE; OXYGENASE;

AMINO ACID SUBSTITUTION; ARTICLE; CATALYSIS; ELECTRON TRANSPORT; ENZYME SUBSTRATE; MUTATION; PROTEIN DOMAIN;

EID: 4444319291     PISSN: 03667022     EISSN: None     Source Type: Journal    
DOI: 10.1246/cl.2004.752     Document Type: Article

References (16)

1. "Nitric Oxide," ed. by B. Mayer, Springer, Berlin (2000).
2. "Nitric Oxide, Biology and Pathobiology," ed. by L. J. Igrarro, Academic Press, San Diego (2000).
3. D. J. Stuehr and S. Ghosh, in "Nitric Oxide," ed. by B. Mayer, Spring, Berlin (2000), pp 33-91.
4. B. S. S. Masters, in "Nitric Oxide, Biology and Pathobiology," ed. by L. J. Ignarro, Academic Press, San Diego, pp 91-104.
5. C. S. Raman, P. Martásek, and B. S. S. Masters, "The Porphyrin Handbook," (2000), Vol. 4, pp 293-339.
6. I. Sagami, Y. Sato, T. Noguchi, M. Miyajima, E. Rozhkova, S. Daff, and T. Shimizu, Coord. Chem. Rev., 226, 179 (2002).
7. T. Shimizu, T. Tateishi, M. Hatano, and Y. Fujii-Kuriyama, J. Biol. Chem., 266, 3372 (1991).
8. T. Shimanuki, H. Sato, S. Daff, I. Sagami, and T. Shimizu, J. Biol. Chem., 274, 26956 (1999).
9. C. S. Raman, H. Li, P. Martásek, V. Král, B. S. S. Masters, and T. L. Poulos, Cell, 95, 939 (1998).
10. B. R. Crain, A. S. Arvai, D. K. Ghosh, C. Wu, E. D. Getzoff, D. J. Stuehr, and J. A. Tainer, Science, 279, 2121 (1998).
11. M. Flinspach, H. Li, J. Jamal, W. Yang, H. Huang, J.-M. Hah, J. A. Gomez-Vidal, E. A. Litzinger, R. B. Silverman, and T. L. Poulos, Nat. Struct. Biol., 11, 54 (2004).
12. I. Sagami, Y. Sato, S. Daff, and T. Shimizu, J. Biol. Chem., 275, 26150 (2000).
13. I. Sagami, S. Daff, and T. Shimizu, J. Biol. Chem., 276, 30036 (2001).
14. E. A. Rozhkova, N. Fujimoto, I. Sagami, S. N. Daff, and T. Shimizu, J. Biol. Chem., 277, 16888 (2002).
15. It appears that functions of the Arg410Leu mutant regarding substrate recognition and NO formation activity are similar to those of the wild-type enzyme. At this moment, it is not clear why these two enzymes have similar functional character. Perhaps, hydrophobic character and length of the side chain of Leu on the molecular surface are suitable for appropriate protein-protein interaction in the dimeric enzyme and thus the Leu mutation may not have largely altered the substrate recognition site. In contrast, those factors of other inactive mutants are different and may have cuased improper folding in the same site.
16. Higher NADPH oxidation rates of the Arg410Ala and Arg410Leu mutants reflect uncoupling of catalysis and electron transfer. Although electron leakage should exit, still certain portions of electrons from the reductase domain are used for catalysis of the Arg410Leu mutant.