title: Binding of 2-hydroxypyridine-N-oxide on dicopper(II) centers: insights into tyrosinase inhibition mechanism by transition-state analogs.
abstract: 2-Hydroxypyridine-N-oxide (HOPNO) is described as a new and efficient transition-state analog (TS-analog) inhibitor for the mushroom tyrosinase with an IC(50) = 1.16 microM and a K(I) = 1.8 microM. Using the binuclear copper(II) complex [Cu(2)(BPMP)(mu-OH)](ClO(4))(2) (2) known as a functional model for the tyrosinase catecholase activity, we isolated and fully characterized a 1:1 (2)/OPNO adduct in which the HOPNO is deprotonated and chelates only one Cu-atom of the binuclear site in a bidentate mode. On the basis of these results, a structural model for the tyrosinase inhibition by HOPNO is proposed.
authors.affiliation: Aix-Marseille Université, Institut des Sciences Moléculaires de Marseille, équipe BiosCiences, iSm2 UMR-CNRS 6263, 13397 Marseille Cedex 20, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Peyroux
authors.forename: Wadih
authors.initials: W
authors.lastname: Ghattas
authors.forename: Renaud
authors.initials: R
authors.lastname: Hardré
authors.forename: Michel
authors.initials: M
authors.lastname: Giorgi
authors.forename: Bruno
authors.initials: B
authors.lastname: Faure
authors.forename: A Jalila
authors.initials: AJ
authors.lastname: Simaan
authors.forename: Catherine
authors.initials: C
authors.lastname: Belle
authors.forename: Marius
authors.initials: M
authors.lastname: Réglier
mesh_terms: D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C547041:2-hydroxypyridine-N-oxide; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D011725:Pyridines; D003300:Copper; D014442:Monophenol Monooxygenase