Binding of 2-hydroxypyridine-N-oxide on dicopper(II) centers: insights into tyrosinase inhibition mechanism by transition-state analogs.
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.
Peyroux
Eugénie
E
Aix-Marseille Université, Institut des Sciences Moléculaires de Marseille, équipe BiosCiences, iSm2 UMR-CNRS 6263, 13397 Marseille Cedex 20, France.
Ghattas
Wadih
W
Hardré
Renaud
R
Giorgi
Michel
M
Faure
Bruno
B
Simaan
A Jalila
AJ
Belle
Catherine
C
Réglier
Marius
M
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
C547041:2-hydroxypyridine-N-oxide; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D011725:Pyridines; D003300:Copper; D014442:Monophenol Monooxygenase