1xiy
From Proteopedia
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Crystal Structure of Plasmodium falciparum antioxidant protein (1-Cys peroxiredoxin)
Overview
Plasmodium falciparum, the causative agent of malaria, is sensitive to oxidative stress and therefore the family of antioxidant enzymes, peroxiredoxins (Prxs) represent a target for antimalarial drug design. We present here the 1.8 A resolution crystal structure of P.falciparum antioxidant protein, PfAOP, a Prx that in terms of sequence groups with mammalian PrxV. The structure is compared to all 11 known Prx structures to gain maximal insight into its properties. We describe the common Prx fold and show that the dimeric PfAOP can be mechanistically categorized as a 1-Cys Prx. In the active site the peroxidatic Cys is over-oxidized to cysteine sulfonic acid, making this the first Prx structure seen in that state. Now with structures of Prxs in Cys-sulfenic, -sulfinic and -sulfonic acid oxidation states known, the structural steps involved in peroxide binding and over-oxidation are suggested. We also describe that PfAOP has an alpha-aneurism (a one residue insertion), a feature that appears characteristic of the PrxV-like group. In terms of crystallographic methodology, we enhance the information content of the model by identifying bound water sites based on peak electron densities, and we use that information to infer that the oxidized active site has suboptimal interactions that may influence catalysis. The dimerization interface of PfAOP is representative of an interface that is widespread among Prxs, and has sequence-dependent variation in geometry. The interface differences and the structural features (like the alpha-aneurism) may be used as markers to better classify Prxs and study their evolution.
About this Structure
1XIY is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin., Sarma GN, Nickel C, Rahlfs S, Fischer M, Becker K, Karplus PA, J Mol Biol. 2005 Mar 4;346(4):1021-34. Epub 2005 Jan 8. PMID:15701514
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