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Cloning and Purification of GST1 in Leishmania tarentolae
Author(s) -
Addy Nicole,
OseiOwusu Nana,
Currington Rashalai,
Hearne Jennifer
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb76
Subject(s) - heme , biochemistry , leishmania , glutathione , biology , enzyme , cloning (programming) , heme oxygenase , chemistry , parasite hosting , world wide web , computer science , programming language
Leishmaniasis afflicts nearly 12 million of the world's population. The causative agent is the Leishmania parasite which, in contrast to other eukaryotes, lacks a complete heme biosynthetic pathway; therefore, they must acquire heme exogenously. Here, we suggest that one mechanism of heme sequestration may be accomplished through its coordination with glutathione (GSH) via membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG), which are members of the glutathione transferase (GST) superfamily. In Macaca fascicularis microsomal prostaglandin E synthase type 2 (mPGES‐2), a MAPEG GST, binds to GSH. This enzyme‐glutathione complex then has the potential to form a coordination bond with heme. Therefore, it is hypothesized that there is an enzyme similar to mPGES‐2 which scavenges free heme in promastigote Leishmania. Consequently, the GST superfamily member gene, resembling mPGES‐2, was identified using genomic searches. The L. tarentolae gene was cloned, facilitating the biophysical and biochemical characterization of the enzyme in relation to its heme binding capabilities. Identification of this gene provides the first evidence of a GST superfamily member in Leishmania. This will be achieved through multiple spectroscopic techniques. Since Leishmania lack a complete heme biosynthetic pathway, the exploitation of its heme dependency is a key target for drug discovery.