Spatial relationship between L-arginine and heme binding sites of endothelial nitric-oxide synthase.

The Journal of Biological Chemistry
V BerkaA L Tsai

Abstract

Binding of L-arginine and imidazole to the endothelial nitric-oxide synthase (eNOS) was characterized by direct heme spectral perturbation. L-Arginine is competitive with imidazole for binding to eNOS. Both equilibrium binding and kinetic binding were measured at 4 and 23 degrees C for these two ligands. Kd (imidazole) is 60 microM and 110 microM, kon (imidazole) is 2.5 x 10(5) M-1 s-1 and 1. 2 x 10(6) M-1 s-1, koff (imidazole) is 11.8 s-1 and 116 s-1 at 4 and 23 degrees C, respectively. Corresponding values for L-arginine are calculated from the data of binding competition with imidazole and computer modeling. Kd (L-arginine) is 0.5 microM and 2.0 microM, kon (L-arginine) is 2 x 10(5) M-1 s-1 and 8 x 10(5) M-1 s-1, koff (L-arginine) is 0.08 s-1 and 1.6 s-1 at 4 and 23 degrees C, respectively. It is suggested that binding of both ligands occurs through the same access channel to the heme site based on their similarly slow association rate constants. A series of potential heme ligands and amino acid analogs of L-arginine were evaluated for their binding and their effect on the heme structure. All ligands besides cyanide tested for binding inhibition are competitive with either L-arginine or imidazole. The space for the distal he...Continue Reading

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S Bredt, S H Snyder
Jun 5, 1987·Journal of Molecular Biology·T L PoulosA J Howard
Oct 27, 1995·Journal of Medicinal Chemistry·J F KerwinP L Feldman
Jan 1, 1994·Annual Review of Nutrition·B S Masters
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·L J RomanB S Masters
Mar 4, 1994·Journal of Molecular Biology·C A HasemannJ Deisenhofer

❮ Previous
Next ❯

Citations

Mar 5, 2004·Microbes and Infection·Iracilda Zeppone CarlosBeatriz Maria Machado de Medeiros
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey K HoldenThomas L Poulos
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·J Vásquez-VivarK A Pritchard
Jul 12, 2011·Free Radical Biology & Medicine·Saptarshi Kar, Mahendra Kavdia
Apr 11, 2003·Journal of Pharmacological Sciences·Kazuya ShinozakiTomio Okamura
Jun 11, 2005·European Journal of Mass Spectrometry·Emily E Jellen, Victor Ryzhov
Aug 24, 1999·The Journal of Biological Chemistry·M NégrerieJ L Martin
Sep 15, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Weiling XuSerpil C Erzurum
Oct 20, 2000·The Journal of Biological Chemistry·J SantoliniD J Stuehr
Nov 16, 2002·Journal of Applied Physiology·Christian K RobertsR James Barnard
Nov 24, 2001·The Journal of Biological Chemistry·Anny Slama-SchwokJean-Louis Martin
Jan 5, 1999·The Journal of Biological Chemistry·P Y HsuL H Wang
Feb 18, 2004·The Journal of Biological Chemistry·Koustubh PandaDennis J Stuehr
Aug 28, 1999·The Journal of Biological Chemistry·B R BabuO W Griffith
Feb 6, 2002·Chembiochem : a European Journal of Chemical Biology·M A NoordermeerJ F Vliegenthart
Nov 6, 2020·Journal of Bone and Mineral Metabolism·Iván Nadir Camal RuggieriSara Feldman
Oct 6, 2001·Nitric Oxide : Biology and Chemistry·S M SmithJ C Salerno
May 1, 2002·Biochemistry·Johannes P M SchelvisAh-Lim Tsai

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.