Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) trapping the αβ dimers of Hb. In turn, the Hp:Hb complexes display heme-based reactivity. Here, the kinetics of cyanide and carbon monoxide dissociation from ferrous-ligated Hp:Hb complexes are reported at pH 7.0 and 20.0 °C. Cyanide dissociation from Hp1-1:Hb(II)-CN- and Hp2-2:Hb-CN- has been followed upon the dithionite-mediated conversion of ferric to ferrous-ligated Hp:Hb complexes. Values of kon for the dithionite-mediated reduction of Hp1-1:Hb(III)-CN- and Hp2-2:Hb(III)-CN- are (7.3 ± 1.1) × 106 M-1 s-1 and (6.2 ± 1.0) × 106 M-1 s-1, respectively. Values of the first-order rate constant (i.e., h) for cyanide dissociation from Hp1-1:Hb(II)-CN- and Hp2-2:Hb(II)-CN- are (1.2 ± 0.2) × 10-1 s-1 and (1.3 ± 0.2) × 10-1 s-1, respectively. CO dissociation from Hp:Hb(II)-CO complexes has been followed by replacing CO with NO. Values of the first-order rate constant (i.e., l) for CO dissociation from Hp1-1:Hb(II)-CO are (1.4 ± 0.2) × 10-2 s-1 and (6.2 ± 0.8) × 10-3 s-1, and those from Hp2-2:Hb(II)-CO are (1.3 ± 0.2) × 10-2 s-1 and (7.3 ± 0.9) × 10-3 s-1. Values of kon, h, and l correspond to those reported for the R-state of tetrameric Hb and isolated α and β chains. This highlights the view that the conformation of the Hb αβ-dimers bound to Hp1-1 and Hp2-2 matches that of the R-state of the Hb tetramer. Furthermore, unlike ferric Hb(III), ligated ferrous Hb(II) does not show an assembly-linked structural change.

Ascenzi, P., De Simone, G., Tundo, G.r., Coletta, M. (2020). Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes. JBIC, 25(3), 351-360 [10.1007/s00775-020-01766-3].

Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes

Tundo G. R.;Coletta M.
2020-01-01

Abstract

Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) trapping the αβ dimers of Hb. In turn, the Hp:Hb complexes display heme-based reactivity. Here, the kinetics of cyanide and carbon monoxide dissociation from ferrous-ligated Hp:Hb complexes are reported at pH 7.0 and 20.0 °C. Cyanide dissociation from Hp1-1:Hb(II)-CN- and Hp2-2:Hb-CN- has been followed upon the dithionite-mediated conversion of ferric to ferrous-ligated Hp:Hb complexes. Values of kon for the dithionite-mediated reduction of Hp1-1:Hb(III)-CN- and Hp2-2:Hb(III)-CN- are (7.3 ± 1.1) × 106 M-1 s-1 and (6.2 ± 1.0) × 106 M-1 s-1, respectively. Values of the first-order rate constant (i.e., h) for cyanide dissociation from Hp1-1:Hb(II)-CN- and Hp2-2:Hb(II)-CN- are (1.2 ± 0.2) × 10-1 s-1 and (1.3 ± 0.2) × 10-1 s-1, respectively. CO dissociation from Hp:Hb(II)-CO complexes has been followed by replacing CO with NO. Values of the first-order rate constant (i.e., l) for CO dissociation from Hp1-1:Hb(II)-CO are (1.4 ± 0.2) × 10-2 s-1 and (6.2 ± 0.8) × 10-3 s-1, and those from Hp2-2:Hb(II)-CO are (1.3 ± 0.2) × 10-2 s-1 and (7.3 ± 0.9) × 10-3 s-1. Values of kon, h, and l correspond to those reported for the R-state of tetrameric Hb and isolated α and β chains. This highlights the view that the conformation of the Hb αβ-dimers bound to Hp1-1 and Hp2-2 matches that of the R-state of the Hb tetramer. Furthermore, unlike ferric Hb(III), ligated ferrous Hb(II) does not show an assembly-linked structural change.
2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
CO dissociation; Cyanide dissociation; Human haptoglobin1-1:hemoglobin complex; Human haptoglobin2-2:hemoglobin complex; Kinetics
Ascenzi, P., De Simone, G., Tundo, G.r., Coletta, M. (2020). Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes. JBIC, 25(3), 351-360 [10.1007/s00775-020-01766-3].
Ascenzi, P; De Simone, G; Tundo, Gr; Coletta, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/245853
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