Download MendeleyCrystal Structure of AhpE from Mycobacterium tuberculosis, a 1-Cys Peroxiredoxin
Li, S., Peterson, N.A., Kim, M.Y., Kim, C.Y., Hung, L.W., Yu, M., Lekin, T., Segelke, B.W., Lott, J.S., Baker, E.N.(2005) J Mol Biol 346: 1035-1046
- PubMed: 15701515
- DOI: https://doi.org/10.1016/j.jmb.2004.12.046
- Primary Citation of Related Structures:
1XVW, 1XXU - PubMed Abstract:
All living systems require protection against the damaging effects of reactive oxygen species. The genome of Mycobacterium tuberculosis, the cause of TB, encodes a number of peroxidases that are thought to be active against organic and inorganic peroxides, and are likely to play a key role in the ability of this organism to survive within the phagosomes of macrophages. The open reading frame Rv2238c in M.tuberculosis encodes a 153-residue protein AhpE, which is a peroxidase of the 1-Cys peroxiredoxin (Prx) family. The crystal structure of AhpE, determined at 1.87 A resolution (R(cryst)=0.179, R(free)=0.210), reveals a compact single-domain protein with a thioredoxin fold. AhpE forms both dimers and octamers; a tightly-associated dimer and a ring-like octamer, generated by crystallographic 4-fold symmetry. In this native structure, the active site Cys45 is in its oxidized, sulfenic acid (S-O-H) state. A second crystal form of AhpE, obtained after soaking in sodium bromide and refined at 1.90 A resolution (R(cryst)=0.242, R(free)=0.286), reveals the reduced structure. In this structure, a conformational change in an external loop, in two of the four molecules in the asymmetric unit, allows Arg116 to stabilise the Cys45 thiolate ion, and concomitantly closes a surface channel. This channel is identified as the likely binding site for a physiological reductant, and the conformational change is inferred to be important for the reaction cycle of AhpE.
Organizational Affiliation:
Centre of Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
