title: Crystal Structure of AhpE from Mycobacterium tuberculosis, a 1-Cys peroxiredoxin.
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.
authors.affiliation: Centre of Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
authors.forename: Simon
authors.initials: S
authors.lastname: Li
authors.forename: Neil A
authors.initials: NA
authors.lastname: Peterson
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Chang-Yub
authors.initials: CY
authors.lastname: Kim
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Hung
authors.forename: Minmin
authors.initials: M
authors.lastname: Yu
authors.forename: Timothy
authors.initials: T
authors.lastname: Lekin
authors.forename: Brent W
authors.initials: BW
authors.lastname: Segelke
authors.forename: J Shaun
authors.initials: JS
authors.lastname: Lott
authors.forename: Edward N
authors.initials: EN
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001965:Bromides / Q000494:pharmacology; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism; D054464:Peroxiredoxins; D011485:Protein Binding; D020836:Protein Structure, Quaternary / Q000187:drug effects; D016415:Sequence Alignment
chemical_list: D001965:Bromides; D010544:Peroxidases; D054464:Peroxiredoxins