title: Identification and initial characterisation of a Plasmodium falciparum Cox17 copper metallochaperone.
abstract: Copper is an essential micronutrient for all living organisms as an important catalytic co-factor for key enzymes. In higher eukaryotes intracellular copper is distributed by copper metallochaperones. Copper chelators such as neocuproine and tetrathiomolybdate inhibit Plasmodium falciparum erythrocytic development, indicating a requirement for copper by the parasite. A screen of the P. falciparum genome database identified eight potential copper-requiring protein orthologs, including four candidate copper metallochaperones implicated in the delivery of copper to cytochrome-c oxidase. A P. falciparum Cox17 ortholog (PfCox17) was recombinantly expressed and the purified protein bound reduced copper in vitro. PfCox17 was localised to the parasite cytoplasm. Characterisation of plasmodial proteins involved in copper metabolism will help us understand the role of this essential microelement in plasmodial homeostasis.
authors.affiliation: Biochemistry, University of KwaZulu-Natal, P.B. X01, Carbis Road, Scottsville 3209, South Africa.
authors.forename: David L
authors.initials: DL
authors.lastname: Choveaux
authors.affiliation: Biochemistry, University of KwaZulu-Natal, P.B. X01, Carbis Road, Scottsville 3209, South Africa.
authors.forename: Robert G E
authors.initials: RG
authors.lastname: Krause
authors.affiliation: Parasitology, Faculty of Biology, Philipps University Marburg, Karl von Frisch Str. 8, D-35043 Marburg, Germany.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
authors.affiliation: Biochemistry, University of KwaZulu-Natal, P.B. X01, Carbis Road, Scottsville 3209, South Africa. Electronic address: goldringd@ukzn.ac.za.
authors.forename: J P Dean
authors.initials: JP
authors.lastname: Goldring
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification*; D002645:Chickens; D016000:Cluster Analysis; D003300:Copper / Q000378:metabolism*; D005260:Female; D006801:Humans; D056511:Metallochaperones / Q000737:chemistry / Q000302:isolation & purification*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D056511:Metallochaperones; D011994:Recombinant Proteins; D003300:Copper; D001205:Ascorbic Acid
keywords: Copper transport; Cox17; Malaria; Metallochaperone; Plasmodium falciparum