Lysine carbonylation is a previously unrecognized contributor to peroxidase activation of cytochrome c by chloramine-T

Abstract

Ion mobility-assisted tandem MS uncovers hitherto overlooked modifications that are critical for the peroxidase activity of chloramine T-modified cytochrome c.

Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochromecand Cardiolipin

“…Notably, the peroxidase activity of Cc increases in a time-dependent manner upon the addition of H 2 O 2 . Such increments in peroxidase activity may result from successive oxidation of M80 and lysine residues, as proposed by Yin and Konermann [80,170]. Indeed, M80 oxidation promotes conformation exchange in Cc which impacts on heme ligation.…”

“…While tyrosine residues can covalently cross-link or undergo oxidation to dihydroxyphenylalanine (DOPA) and subsequently to quinones, lysine residues can undergo carbonylation [152,168,169]. These changes occur when H 2 O 2 is added to Cc samples [80,152,[170][171][172][173].…”

“…As discussed before, Cc is modulated by several oxidative modifications due to its activity, eventually leading to changes in iron coordination. One oxidative modification is the carbonylation of lysine residues, which affects residues 72 and 73, both of which are involved in the alkaline transition of Cc [170] (Figure 5). Reportedly, successive carbonylation events at K53, K55, K72, and K73 lead to the formation of the pentacoordinated Cc species, resulting in increased Cc peroxidase activity (Table 1) [170].…”

“…One oxidative modification is the carbonylation of lysine residues, which affects residues 72 and 73, both of which are involved in the alkaline transition of Cc [170] (Figure 5). Reportedly, successive carbonylation events at K53, K55, K72, and K73 lead to the formation of the pentacoordinated Cc species, resulting in increased Cc peroxidase activity (Table 1) [170]. Similarly, the sulfoxidation of M80 facilitates the formation of a Compound I-type intermediate that initiates the activity of Cc peroxidase (Table 1) The point mutations Y48H and G41S in Cc cause the appearance of a special type of thrombocytopenia (thrombocytopenia 4) which is an asymptomatic disorder [199,200].…”

A Review on Recognition of Various Peroxidases

“…Cytochrome C peroxidase (CCP) is a POD that catalyzes the reaction of hydrogen peroxide to oxidize cytochrome C, which plays a key role in the process of apoptosis [39]. In catalysis, when peroxide existed, electron transfers from cytochrome C to CCP and forms an intermediate similar to the compoundⅠin HRP catalysis, which is the Trp191 indole cation free radical [CCPFe(IV)=OTrp191 + ], being the main active intermediate of CCP-catalytic oxidation substrate.…”