Human ceruloplasmin. Intramolecular electron transfer kinetics and equilibration.
Pulse radiolytic reduction of disulfide bridges in ceruloplasmin yielding RSSR(-) radicals induces a cascade of intramolecular electron transfer (ET) processes. Based on the three-dimensional structure of ceruloplasmin identification of individual kinetically active disulfide groups and type 1 (T1) copper centers, the following is proposed. The first T1 copper(II) ion to be reduced in ceruloplasmin is the blue copper center of domain 6 (T1A) by ET from RSSR(-) of domain 5. The rate constant is 28 +/- 2 s(-1) at 279 K and pH 7.0. T1A is in close covalent contact with the type 3 copper pair and indeed electron equilibration between T1A and the trinuclear copper center in the domain 1-6 interface takes place with a rate constant of 2.9 +/- 0.6 s(-1). The equilibrium constant is 0.17. Following reduction of T1A Cu(II), another ET process takes place between RSSR(-) and T1B copper(II) of domain 4 with a rate constant of 3.9 +/- 0.8. No reoxidation of T1B Cu(I) could be resolved. It appears that the third T1 center (T1C of domain 2) is not participating in intramolecular ET, as it seems to be in a reduced state in the resting enzyme.
Farver
O
O
Institute of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, DK-2100 Copenhagen O, Denmark. of@mail.dfh.dk
Bendahl
L
L
Skov
L K
LK
Pecht
I
I
D002570:Ceruloplasmin / Q000737:chemistry*; D004579:Electron Transport; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis
D002570:Ceruloplasmin