title: Structural insights into thioredoxin-2: a component of malaria parasite protein secretion machinery.
abstract: Thioredoxins are vital components of Plasmodium proteome and act as both reducing agents and protein disulfide reductases. The malaria parasite P. falciparum thioredoxin-2 (PfTrx-2) is part of the multi-protein complex embedded within the parasite parasitophorous vacuolar membrane (PVM) which purportedly directs protein secretion. We have characterized structural and enzymatic features of PfTrx-2, and we show that PfTrx-2 adopts a canonical thioredoxin fold but with significant structural differences in its N-terminus. Our confocal localization data suggest distinct PVM residency of PfTrx-2. Based on the crystal structure of PfTrx-2, we screened and tested small molecule drug-like libraries for compounds which target unique structural features of PfTrx-2. Disruption of PfTrx-2 interactions using specific inhibitors may result in a dysfunctional parasite translocon that is rendered unable to secrete pathogenic proteins into hosts. This approach therefore offers a new focus for anti-malarial drug development.
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi, 110067,  India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Sharma
authors.forename: Arvind
authors.initials: A
authors.lastname: Sharma
authors.forename: Sameer
authors.initials: S
authors.lastname: Dixit
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013499:Surface Properties; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: D015800:Protozoan Proteins; D011994:Recombinant Proteins; D013879:Thioredoxins