Di-haem cytochrome C peroxidase superfamily

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Last update: 2021-12-02 (Bruno Savelli)

Di-haem cytocthrome c peroxidase (DiHCcP)
Methylamine utilisation protein (MauG)
Other di-haem peroxidase (DiHPOX)


This two haem containing protein, as well as other cytochrome c peroxidases, reduce hydrogen peroxide to water using c-type haem as an oxidisable substrate. The protein is structured into two domains, each containing one c-type haem group, with a calcium-binding site at the domain interface. This family also includes MauG proteins, whose similarity to di-haem CCP was previously recognised (Gak et al., 1997; Fulop et al., 1995). The 6 sequences (3 DiHCcP and 3 MauG) shown in the article of Wang et al. (2003) have been used as templates for the first sequence search. Particular attention has been made on: - the presence of the His residue located 16 a.a. after the first CxxCH motif at the N-term. - the presence of the Met residue located at the end of the sequence (PYFHxGxxxxLxxAVxxM)

Both residues are important for the cytochrome c peroxidase activity of the protein (Dias et al., 2004). The histidine is bound to the low-potential haem in the inactive form. It is then released for activation of the enzyme to allow access to hydrogen peroxide. The methionine is bound to the high-potential haem both in the active and inactive forms.

MauG: no consensus motif exists so far. Only the proteins regrouped in a mau cluster (mauFBEDACJGLMN) (Li et al., 2006; Chistoserdov et al., 2001) have been considered as MauG. MauG proteins have a very low peroxidase activity (Wang et al., 2003). They are rather monooxygenases that play an important role in the synthesis of a cofactor (tryptophan tryptophylquinone, TTQ) for the methylamine dehydrogenase (MADH) protein (Li et al., 2006).

DiHCcP: sequences not detected as member of a mau cluster have been included in this independant class. They show high homology with the "real" Maug and they have annotated most of the time as MauG in Swiss-Prot/TREMBL. Some DiHCcP have been entered that lack the critical His. Some even lack both the critical His and Met residues. Due to sequence homology, these sequences have been entered under the appellation DiHCcP. In the remarks field, absence of His/Met has been noted.

DiHPOX: This category has not been recognised so far in the literature. In RedoxiBase, all the di-haem peroxidases that cannot be included in the classes DiHCcP and MauG are grouped together. Usually, they do not contain the critical His and Met residues, and their sequence identity to DiHCcP and MauG is very low (they form one separate group in a phylogenetic tree). Their function is unknown.


Pfam : PF03150
InterPro : IPR004852
Di-haem cytochrome c peroxidase.

The profiles do not make a distinction between DiHCcP, MauG and DiHPOX.


Gak ER, Tsygankov YD, Chistoserdov AY. Organization of methylamine utilization genes (mau) in Methylobacillus flagellatum KT and analysis of mau mutants. Microbiology. 1997 Jun;143 (Pt 6):1827-35. PMID: 9202457
Fulop V, Ridout CJ, Greenwood C, Hajdu J. Crystal structure of the di-haem cytochrome c peroxidase from Pseudomonas aeruginosa. Structure. 1995 Nov 15;3(11):1225-33. PMID: 8591033
Chistoserdov, AY. Cloning, sequencing and mutagenesis of the genes for aromatic amine dehydrogenase from Alcaligenes faecalis and evolution of amine dehydrogenases. Microbiology. 2001 Aug;147(Pt 8):2195-202. PMID: 11495996
Dias JM, Alves T, Bonifacio C, Pereira AS, Trincao J, Bourgeois D, Moura I, Romao MJ. Structural basis for the mechanism of Ca2+ activation of the di-heme cytochrome c peroxidase from Pseudomonas nautica 617. Structure. 2004 Jun;12(6):961-73. PMID: 15274917
Li X, Jones LH, Pearson AR, Wilmot CM, Davidson VL. Mechanistic Possibilities in MauG-Dependent Tryptophan Tryptophylquinone Biosynthesis. Biochemistry 2006 Nov 7;45(44):13276-83. PMID: 17073448.
Wang Y, Graichen ME, Liu A, Pearson AR, Wilmot CM, Davidson VL. MauG, a Novel Diheme Protein Required for Tryptophan Tryptophylquinone Biogenesis. Biochemistry 2003 Jun 24;42(24):7318-25. PMID: 12809487