3UL3

Structural insights into thioredoxin-2: a component of malaria parasite protein secretion machinery

Summary for 3UL3

• Entry DOI: 10.2210/pdb3ul3/pdb
• Descriptor: Thioredoxin (2 entities in total)
• Functional Keywords: thioredoxin, ptex, oxidoreductase
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 2
• Total formula weight: 30067.50

Authors

Sharma, A.,Sharma, A.,Dixit, S.,Sharma, A. (deposition date: 2011-11-10, release date: 2011-12-14, Last modification date: 2024-03-20)

Primary citation

Sharma, A.,Sharma, A.,Dixit, S.,Sharma, A.
Structural insights into thioredoxin-2: a component of malaria parasite protein secretion machinery.
Sci Rep, 1:179-179, 2011

PubMed 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.

PubMed: 22355694
DOI: 10.1038/srep00179

Experimental method

X-RAY DIFFRACTION (2.905 Å)