title: Expression and biochemical characterization of a type I methionine aminopeptidase of Plasmodium vivax.
abstract: Methionine aminopeptidases (MetAPs), ubiquitous enzymes that play an important role in nascent protein maturation, have been recognized as attractive targets for the development of drugs against pathogenic protozoa including Plasmodium spp. Here, we characterized partial biochemical properties of a type I MetAP of Plasmodium vivax (PvMetAP1). PvMetAP1 had the typical amino acid residues essential for metal binding and substrate binding sites, which are well conserved in the type I MetAP family enzymes. Recombinant PvMetAP1 showed activity in a broad range of neutral pHs, with optimum activity at pH 7.5. PvMetAP1 was stable under neutral and alkaline pHs, but was relatively unstable under acidic conditions. PvMetAP1 activity was highly increased in the presence of Mn(2+), and was effectively inhibited by a metal chelator, EDTA. Fumagillin and aminopeptidase inhibitors, amastatin and bestatin, also showed an inhibitory effect on PvMetAP1. The enzyme had a highly specific hydrolytic activity for N-terminal methionine. These results collectively suggest that PvMetAP1 belongs to the family of type I MetAPs and may play a pivotal role for the maintenance of P. vivax physiology by mediating protein maturation and processing of the parasite.
authors.affiliation: Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Kang
authors.affiliation: Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong 363-951, Republic of Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Ju
authors.affiliation: Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong 363-951, Republic of Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Ju
authors.affiliation: Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Institute of Health Sciences and PMBBRC, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Kon Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong 363-951, Republic of Korea.
authors.forename: Won-Ja
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.affiliation: Department of Tropical Medicine, and Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon 400-712, Republic of Korea.
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Parasitology and Tropical Medicine, and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea. Electronic address: bkna@gnu.ac.kr.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
mesh_terms: D015870:Gene Expression; D007930:Leucine / Q000031:analogs & derivatives / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D063208:Methionyl Aminopeptidases / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000737:chemistry; D010966:Plasmodium vivax / Q000201:enzymology* / Q000235:genetics; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D008345:Manganese; C016977:amastatin; D063208:Methionyl Aminopeptidases; D007930:Leucine; C012211:ubenimex
keywords: Drug target; Fumagillin; Methionine aminopeptidase; Plasmodium vivax