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Atypical Caseinolytic Protease Homolog From Plasmodium Falciparum Possesses Unusual Substrate Preference and a Functional Nuclear Localization Signal

Atypical Caseinolytic Protease Homolog From Plasmodium Falciparum Possesses Unusual Substrate Preference and a Functional Nuclear Localization Signal

Wenjie Lin, Maurice Chan, Tiow-Suan Sim

Parasitol Res. 2009 Nov;105(6):1715-22.

PMID: 19789896

Abstract:

Although ATP-dependent caseinolytic protease (Clp) complexes are important for regulating the pathogenicity, survival, and development of many pathogens, their physiological roles in the pathogenicity of malarial parasites remain unknown. This study reports the cloning, authentication, and characterization of a putative Clp protease subunit from Plasmodium falciparum (PfClpP). Heterologous expression studies showed that signal peptide hindered the soluble expression of the full-length PfClpP. Biochemical analyses of the recombinant PfClpP showed that it did not cleave the known ClpP substrate, succinyl-leucine-tyrosine-7-amido-4-methylcoumarin hydrochloride (AMC). Instead, PfClpP readily hydrolyzed a different substrate, glycine-arginine-AMC. The distinctive substrate preference of PfClpP suggests structural uniqueness in its substrate-binding sites that might be exploitable in anti-malarial drug development. Whether PfClpP resembles most eukaryotic ClpPs in being localized to the mitochondria and chloroplasts was also investigated using a mammalian surrogate host system. The results observed showed that green-fluorescence protein tagged PfClpP proteins were localized to the nucleus. PfClpP may have a unique and specialized role in the plasmodial nucleus. Taken together, this study has shown that PfClpP has a unique peptide cleavage function that is localized at the plasmodial nucleus, probably positioned to elicit a regulatory role in the parasite's pathogenicity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP70375223	Z-L-Arg 7-amido-4-methylcoumarin hydrochloride		70375-22-3	Price
AP94099577	L-Tyrosine 7-amido-4-methylcoumarin		94099-57-7	Price

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