6erc
Peroxidase A from Dictyostelium discoideum (DdPoxA)Peroxidase A from Dictyostelium discoideum (DdPoxA)
Structural highlights
Publication Abstract from PubMedOxidation of halides and thiocyanate by heme peroxidases to antimicrobial oxidants is an important cornerstone in the innate immune system of mammals. Interestingly, phylogenetic and physiological studies suggest that homologous peroxidases are already present in mycetozoan eukaryotes such as Dictyostelium discoideum This social amoeba kills bacteria via phagocytosis for nutrient acquisition at its single-cell stage and for antibacterial defense at its multicellular stages. Here we demonstrate that peroxidase A from D. discoideum (DdPoxA) is a stable, monomeric, glycosylated and secreted heme peroxidase with homology to mammalian peroxidases. The first crystal structure (2.5 A resolution) of a mycetozoan peroxidase of this superfamily shows the presence of a posttranslationally-modified heme with one single covalent ester bond between the 1-methyl heme substituent and E236. The metalloprotein follows the halogenation cycle, whereby Compound I oxidizes iodide and thiocyanate at high (> 10(8) M(-1) s(-1)) and bromide at very low rates. It is demonstrated that DdPoxA is upregulated and likely secreted at late multicellular development stages of D. discoideum when migrating slugs differentiate into fruiting bodies that contain persistent spores on top of a cellular stalk. Expression of DdPoxA is shown to restrict bacterial contamination of fruiting bodies. Structure and function of DdPoxA are compared to evolutionary related mammalian peroxidases in the context of non specific immune defense. Secreted Heme Peroxidase from Dictyostelium discoideum: Insights into Catalysis, Structure and Biological Role.,Nicolussi A, Dunn JD, Mlynek G, Bellei M, Zamocky M, Battistuzzi G, Djinovic-Carugo K, Furtmuller PG, Soldati T, Obinger C J Biol Chem. 2017 Dec 14. pii: RA117.000463. doi: 10.1074/jbc.RA117.000463. PMID:29242189[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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