Cytochrome c Peroxidases

Armstrong FA, Bond AM, Buchi FN, Hanmett A, Hill HAO, Lannon AM, Lettington OC, Zoski CG. 1993. Electrocatalytic reduction of hydrogen-peroxide at a stationary pyrol3ftic-graphite electrode surface in the presence of cytochrome-c peroxidase— A description based on a microelectrode array model for adsorbed enzyme molecules. Analyst 118 973-978. 

Ivancich, A., P. Dorlet et al. (2001). Multifrequency high-field EPR study of the tryptophanyl and tyrosyl radical intermediates in wild-type and the W191G mutant of cytochrome c peroxidase. J. Am. Chem. Soc. 123 5050-5058. 

Enzymes Cytochrome cdi Nitrate and Cytochrome c Peroxidase Vilmos Fulop, Nicholas J. Watmough, and Stuart J. Ferguson... 

Peroxidases have also been utilized for preparative-scale oxidations of aromatic hydrocarbons. Procedures have been optimized for hydroxylation of l-tyrosine, D-(-)-p-hydroxyphenylglycine, and L-phenylalanine by oxygen, di-hydroxyfumaric acid, and horseradish peroxidase (89). Lactoperoxidase from bovine milk and yeast cytochrome c peroxidase will also catalyze such hydroxylation reactions (89). 

Okuda K, Mashino T, Hirobe M (1996) Superoxide radical quenching and cytochrome C peroxidase-like activity of C60-dimalonic acid, C62(COOH)4. Bioorg. Med. Chem. Lett. 6 539-542. 

H. Koloczek, T. Horie, T. Yonetani, H. Anni, G. Maniara, and J. M. Vanderkooi, Interaction between cytochrome c and cytochrome c peroxidase Excited-state reactions of zinc- and tin-substituted derivatives, Biochemistry 26, 3142-3148 (1987). 

Cytochrome c peroxidase domain 1 C. Miscellaneous antiparallel a Carp muscle calcium-binding protein Egg lysozyme Citrate synthase Catalase domain 2 Cytochrome c peroxidase domain 2 p-Hydroxybenzoate hydroxylase domain 3 II. Parallel a/j3 domains... 

Cytochrome cra (Almassy and Dickerson, 1978), see Cytochrome c Cytochrome cH5 (Korszun and Salemme, 1977), see Cytochrome c Cytochrome c peroxidase (Poulos et al., 1980)... 

Pancreatic ribonuclease Staphylococcal nuclease Peroxidases Glutathione peroxidase Cytochrome c peroxidase Oxygen carriers Myoglobin, hemoglobin Myohemerythrin, hemerythrin Hormone-binding proteins Uteroglobin Pre albumin Lectins... 

A Chapter of this volume is devoted to these techniques, which are merely illustrated in this section by one particular example. The electron transfer system that is the most intensively submitted to genetic manipulations is certainly the physiological complex between yeast cytochrome c and peroxide-oxidized cytochrome c peroxidase, which presents many advantages [143], Among the modifications performed on cytochrome c peroxidase, one may mention the substitution of Trp 191 which interacts directly with His 175 of the heme [144], and of His 181 [145] which was proposed as a bridging unit in a superexchange path involving Phe 87 of cytochrome c [136,146]. On the cytochrome c side, Phe 87 las been substituted [147], as well as other residues expected to play an important role in the stabilization of the noncovalent complex [143]. 

The standard formalisms for describing ET processes assume that in reactions such as Eqs. (1) and (2) there is but a single stable conformational form for each of the precursor and successor electron-transfer states. However, for a system that displays two (or more) alternative stable conformations with different ET rates, dynamic conformational equilibrium can modulate the ET rates. Major protein conformational changes can occur at rates that are competitive with observed rates of ET [9], and such gating [10] may occur in non-rigid complexes such as that between zinc cytochrome c peroxidase (ZnCcP) and cytochrome c (see below) or even within cytochrome c [5]. 

Cytochrome c and cytochrome c peroxidase (ccp) are physiological partners in the ccp reaction cycle structural, thermodynamic, and kinetic data are available for the protein-protein interaction [69-72]. A model indicates that the cyt c/ccp complex is stabilized by specific salt bridges with the hemes in parallel planes the Fe-Fe distance is 24 A, and the edge-edge distance is 16 A [70]. 

Steady state kinetics and protein-protein binding measurements have also been reported for the interaction of these mutant cytochromes with bovine heart cytochrome c oxidase [120]. The binding of cytochrome c variants to the oxidase occurred with increasing values of Kj in the order He (3 x 10 Mol L ) < Leu = Gly < wild-type < Tyr < Ser (3 x 10 molL ). Steady-state kinetic analysis indicated that the rate of electron transfer with cytochrome c oxidase increased in the order Ser < He < Gly < Leu < Tyr < wild-type, an order notably different from that observed for a related analysis of the oxidation of these mutants by cytochrome c peroxidase [85]. This difference in order of mutant turnover by the oxidase and peroxidase may arise from differences in the mode of interaction of the cytochrome with these two enzymes. 

As part of a subsequent study concerning primarily second-site revertant yeast iso-l-cytochrome c variants, Hazzard et al. evaluated the effect of converting Lys-72 to an aspartyl residue by site-directed mutagenesis on the electron transfer kinetics of the cytochrome c-cytochrome c peroxidase complex [136]. Lys-72 was of interest for this purpose, because it is involved in the hypothetical model for the complex formed by these two proteins that was proposed by Poulos and Kraut on the basis of molecular graphics docking [106]. In these... 

In order to relate structure and function at a more direct level, it is necessary to focus on systems which have better characterized structure than the complex membrane bound proteins like cyt c oxidase. One particularly useful paradigm in this context is the cytochrome c-cytochrome c peroxidase couple [18]. Cep is not involved in electron transport, per se its apparent function [19] is detoxification of hydrogen peroxide via the sequence H2O2 -I- cep Fe(III) -> H2O -I- cep Fe(IV) O (protein) compound ES ... 

First the structures of cytochrome cytochrome c peroxidase [21] are both known at high resolution. Although the precise three dimensional structure of the protein-protein complex is unknown (and, we shall argue, unknowable), molecular modeling has produced detailed stereochemical models for the c ccp complex which are subject to experimental testing and subsequent improvement, as detailed below. 

---