PDBsum entry 1xiy

Oxidoreductase

PDB id: 1xiy

Contents

Protein chains

172 a.a. *

Waters ×277

* Residue conservation analysis

PDB id:

1xiy

Name:

Oxidoreductase

Title:

Crystal structure of plasmodium falciparum antioxidant protein (1-cys peroxiredoxin)

Structure:

Peroxiredoxin. Chain: a, b. Fragment: residues 60-240. Synonym: pfaop. Engineered: yes

Source:

Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.187 R-free: 0.218

Authors:

G.N.Sarma,M.Fischer,C.Nickel,K.Becker,P.A.Karplus

Key ref:

G.N.Sarma et al. (2005). Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin. J Mol Biol, 346, 1021-1034. PubMed id: 15701514 DOI: 10.1016/j.jmb.2004.12.022

Date:

22-Sep-04 Release date: 15-Feb-05

Protein chains

Q5MYR6  (Q5MYR6_PLAF7) -  1-cys peroxiredoxin from Plasmodium falciparum (isolate 3D7)

Seq: 240 a.a.

Struc: 172 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.11.1.15 - Transferred entry: 1.11.1.24, 1.11.1.25, 1.11.1.26, 1.11.1.27, 1.11.1.28
• Pathway: Peroxiredoxin
• Reaction: 2 R'-SH + ROOH = R'-S-S-R' + H₂O + ROH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jmb.2004.12.022

J Mol Biol 346:1021-1034 (2005)

PubMed id: 15701514

Crystal structure of a novel Plasmodium falciparum 1-Cys peroxiredoxin.

G.N.Sarma, C.Nickel, S.Rahlfs, M.Fischer, K.Becker, P.A.Karplus.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Figure 1. Electron density map quality and active site structure. A stereoview of the 2F[o] -F[c] electron density map contoured at 1.5 r[rms] shows clear density for the cysteine sulfonic acid (C[P]59) of monomer A. Atoms C[P]59-Od2 and -Od3 are identified, and Od1, the third C[P] oxygen atom, is not labeled due to space. Three ordered water sites, the residues, and the secondary structures contributing to the active site are also labeled. Electron density for Wat179 appears at a lower contour level of 1.3 r[rms]. Hydrogen bonds are indicated by broken gray lines and the close approach of Thr-Og to C[P]59-Od1 by red dotted lines. The view is similar to that of the upper monomer in Figure 2. The Figure was prepared using Bobscript65 and Raster3D.66

Figure 5.
Figure 5. An a-aneurism near the active site of PfAOP. The C^a atoms of the a2-helix of PfAOP (blue), human PrxV (green), AhpC (red), and PrxII (light brown) are overlaid to illustrate the a-aneurism in PfAOP and human PrxV. A shaded and a transparent circle indicate the position of the a-aneurism and the Pro residue conserved in PrxV-like Prxs, respectively. The PfAOP atoms are labeled and their , q angles are noted in parentheses. The , q angles of human PrxV are all within 20° of those of PfAOP. The hydrogen bonding patterns and the torsion angles in PfAOP and human PrxV are very similar to those described for the prototypical a-aneurism.51 The Figure was prepared using MOLSCRIPT65 and Raster3D.66

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 346, 1021-1034) copyright 2005.

Figures were selected by an automated process.