title: Nitric oxide (NO) traffic in endothelial NO synthase. Evidence for a new NO binding site dependent on tetrahydrobiopterin?
abstract: Nitric oxide (NO) traffic within the reduced ferrous-nitrosyl complex of endothelial nitric-oxide synthase (eNOS) has been studied by ultrafast time-resolved absorption spectroscopy. In the presence of tetrahydrobiopterin, the rate of NO rebinding to the heme upon photodissociation depends on the NO concentration. The time scale of this process, picoseconds to nanoseconds, precludes a diffusion from the solution toward the protein medium, and altogether the data point at a new NO binding site within the protein. Comparison of the kinetics of pterin-bound and -depleted eNOS points out that the existence of this new site depends on the presence of tetrahydrobiopterin. The new non-heme site may act as a "doorstep" to the heme pocket and control NO escape from eNOS.
authors.affiliation: Laboratory for Optics and Biosciences, INSERM U451, CNRS Unité Mixte de Recherche 7645, Ecole Polytechnique, 91128 Palaiseau, France. anny.schwok@polytechnique.fr
authors.forename: Anny
authors.initials: A
authors.lastname: Slama-Schwok
authors.forename: Michel
authors.initials: M
authors.lastname: Négrerie
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berka
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lambry
authors.forename: Ah-Lim
authors.initials: AL
authors.lastname: Tsai
authors.forename: Marten H
authors.initials: MH
authors.lastname: Vos
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Martin
mesh_terms: D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000737:chemistry* / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D001708:Biopterins; D009569:Nitric Oxide; D006418:Heme; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin