4b1b
Crystal structure of Plasmodium falciparum oxidised Thioredoxin Reductase at 2.9 angstrom
Structural highlights
FunctionTRXR_PLAF7 Catalyzes the transfer of electrons from NADPH to thioredoxins TRX1, TRX2 and TRX3, which in turn act as reductants of disulfide containing proteins (PubMed:9368022, PubMed:11013257, PubMed:16910770, PubMed:23845423). Able to reduce nitroglutathione (GSNO), a compound involved in the transport of nitric oxide (NO); however, TRX1 is more efficient in reducing GSNO (PubMed:11013257). Has no catalytic activity towards oxidized glutathione (GSSG) (PubMed:11013257).[1] [2] [3] [4] Publication Abstract from PubMedPlasmodium falciparum is the vector of the most prevalent and deadly form of malaria, and, among the Plasmodium species, it is the one with the highest rate of drug resistance. At the basis of a rational drug design project there is the selection and characterization of suitable target(s). Thioredoxin reductase, the first protection against reactive oxygen species in the erythrocytic phase of the parasite, is essential for its survival. Hence it represents a good target for the design of new anti-malarial active compounds. In this paper we present the first crystal structure of recombinant P. falciparum thioredoxin reductase (PfTrxR) at 2.9A and discuss its differences with respect to the human orthologue. The most important one resides in the dimer interface, which offers a good binding site for selective non competitive inhibitors. The striking conservation of this feature among the Plasmodium parasites, but not among other Apicomplexa parasites neither in mammals, boosts its exploitability. Crystal structure of Plasmodium falciparum thioredoxin reductase, a validated drug target.,Boumis G, Giardina G, Angelucci F, Bellelli A, Brunori M, Dimastrogiovanni D, Saccoccia F, Miele AE Biochem Biophys Res Commun. 2012 Aug 6. PMID:22889878[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
