期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 346, 期 4, 页码 1035-1046出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2004.12.046
关键词
peroxiredoxin; Mycobacterium tuberculosis; antioxidant; crystal structure; redox mechanism
资金
- NIGMS NIH HHS [P50-GM062410] Funding Source: Medline
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 Angstrom 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 Angstrom 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. (C) 2004 Elsevier Ltd. All rights reserved.
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