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Entamoeba Histolytica: Biochemical Characterization of a Protein Disulfide Isomerase

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The oxidation and correct formation of disulfide bonds is an important biochemical modification of many proteins. Early observations showed that disulfide bond formation proceeds much faster in vivo than in vitro, suggesting the existence of a catalyst for protein oxidative folding in living cells [1]. Protein disulfide isomerase (PDI, EC 5.3.4.1) is a eukaryotic oxidoreductase that catalyzes the oxidation, reduction, and isomerization of disulfide bonds in nascent polypeptides [2]. The subcellular localization and its function suggest that PDI plays a key role in the folding of proteins delivered to the secretory pathway [3]. For the protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, the accurate formation of disulfide bonds is an important biochemical modification required for the correct folding of some proteins, including proteins involved in the adhesion and destruction of human tissues. Amebic proteins such as the Gal/GalNAc-inhibitable lectin and the pore-forming peptides have disulfide bonds which are crucial for the acquisition of their active conformation [4, 5]. Thus, the identification and characterization of amebic enzymes that play key roles in protein folding is essential to understand this biochemical process and gain insight knowledge of the cell biology of this parasite. An entamoebal PDI enzyme (EhPDI) that exhibits oxidative refolding activity in vivo as well as oxidative and reductive activities in vitro has been identified [6, 7]. Structurally, EhPDI shares domain architecture with the Dictyostelium discoideum homologue, DdPDI [8], featuring two active thioredoxin domains and a D-domain (also known as Erp29c domain). Interestingly, both enzymes lack the canonical ER-retenti... ... middle of paper ... ...zolides, Exp. Parasitol. (2008) 80-88. [22] T. Kimura, Y. Hosoda, Y. Kitamura, H. Nakamura, T. Horibe, M. Kikuchi, Functional differences between human and yeast protein disulfide isomerase family proteins, Biochem. Bioph. Res. Co. 320 (2004) 359-365. [23] C.W. Gruber, M. Cemazar, B. Heras, J.L Martin, D.J. Craik, Protein disulfide isomerase: the structure of oxidative folding, Trends Biochem. Sci. 31 (2006) 455-464. [24] M.A. Ramos, R.E. Mares, P.D. Magaña, J.E. Ortega, J.M. Cornejo-Bravo, In silico identification of the protein disulfide isomerase family from a protozoan parasite, Comput. Biol Chem. 32 (2008) 66-70. [25] D.R. Boettner, C.D. Huston, A.S. Linford, S.N. Buss, E. Houpt, N.E. Sherman, W.A. Petri Jr., 2008. Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family, PLoS Pathog. 4 (2008) e8.
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