This subfamily is named after human PrxV; this protein has a C-terminal peroxisome targeting sequence and can be expresed with or without an N-terminal mitochondrial signal sequence, and has been found in multiple locations including mitochondria, peroxisomes, and cytoplasm (Knoops et al. 2007). Members of this subfamily have been referred to as the “D” group (Echalier et al. 2005; Trivelli et al. 2003), as part of the “Prx3” group (Copley et al. 2004), and plant type II Prxs (Dietz 2003). Based upon the clear homology in the Prx portion of the protein, we also include the bacterial Prx5-glutaredoxin (Grx) fusion proteins as part of the Prx5 subfamily. Prx5 subfamily members are present across the phylogenetic spectrum and are found from bacteria to mammals with members present in plants, fungi, and yeast (Hofmann et al. 2002).
Members of the Prx5 proteins form redox-insensitive A-type dimers and include 1-Cys Prxs as well as Prxs with a resolving cysteine on the same subunit as its partner peroxidatic cysteine (i.e., atypical 2-Cys) (Hall et al. 2010; Sarma et al. 2005). With the possible exception of the bacterial subfamily members fused to Grx, the reductant for Prx5 subfamily members is typically thioredoxin (Trx). Human PrxV is somewhat less reactive with hydrogen peroxide than PrxI and PrxII, but is very efficient with organic hydroperoxides (Trujillo et al. 2007a) and peroxinitrite (Trujillo 2007b).
Aligned active site signatures (from DASP; Nelson et al. 2011) from the Prx5 subfamily (center group) and one representative each of the other five subfamilies (upper and lower groups). Key residues of the active site signatures are noted by asterisks along the top. Shown below is the unrooted tree generated by Phylip’s Drawtree using the SDSC Biology Workbench tools.
12 structures, 5 proteins
PDB identifiers
Name
Species
1hd2, 1urm, 1h4o, 1oc3, 2vl2, 2vl3, 2vl9, 3mng
Prx5
Homo sapiens
1tp9
PrxD
Populus tremula
1nm3
PrxV
Haemophilus influenzae
2pwj
Type 2 F
Pisum sativum
1xiy
pfAOP
Plasmodium falciparum
Prx5 references
Copley, S. D., Novak, W. R. P., & Babbitt, P. C. (2004). Divergence of function in the thioredoxin fold suprafamily: evidence for evolution of peroxiredoxins from a thioredoxin-like ancestor. Biochemistry, 43(44), 13981-13995. PMID: 15518547
Dietz, K. (2003). Plant peroxiredoxins. Annual Review of Plant Biology, 54, 93-107. PMID: 14502986
Echalier, A., Trivelli, X., Corbier, C., Rouhier, N., Walker, O., Tsan, P., Jacquot, J., et al. (2005). Crystal structure and solution NMR dynamics of a D (type II) peroxiredoxin glutaredoxin and thioredoxin dependent: a new insight into the peroxiredoxin oligomerism. Biochemistry, 44(6), 1755-1767. PMID: 15697201
Knoops, B., Loumaye, E., & Van Der Eecken, V. (2007). Evolution of the peroxiredoxins. In L. Flohé and J. R. Harris, (Eds.), Peroxiredoxin Systems. (pp. 27-40). New York: Springer.PMID: 18084888
Nelson, K. J., Knutson, S. T., Soito L., Klomsiri C., Poole, L. B., & Fetrow, J. S. (2011). Analysis of the peroxiredoxin family: using active site structure and sequence information for global classification and residue analysis. Proteins, 79(3), 947-964. PMID: 21181731
Sarma, G. N., Nickel, C., Rahlfs, S., Fischer, M., Becker, K., & Karplus, P. A. (2005). Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin. Journal of Molecular Biology, 346(4), 1021-1034.PMID: 15701514
Trivelli, X., Krimm, I., Ebel, C., Verdoucq, L., Prouzet-Mauléon, V., Chartier, Y., Tsan, P., et al. (2003). Characterization of the yeast peroxiredoxin Ahp1 in its reduced active and overoxidized inactive forms using NMR. Biochemistry, 42(48), 14139-14149. PMID: 14640681
Trujillo, M., Clippe, A., Manta, B., Ferrer-Sueta, G., Smeets, A., Declercq, J., Knoops, B., et al. (2007a). Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation. Archives of Biochemistry and Biophysics, 467(1), 95-106. PMID: 17892856
Trujillo, M., Ferrer-Sueta, G., Thomson, L., Flohé, L., & Radi, R. (2007b). Kinetics of peroxiredoxins and their role in the decomposition of peroxynitrite. In L. Flohé and J. R. Harris, (Eds.), Peroxiredoxin Systems. (pp. 83-113). New York: Springer. Retrieved from PMID: 18084891
