Details

Autor(en) / Beteiligte

• Jönsson, Thomas J
• Murray, Michael S
• Johnson, Lynnette C
• Poole, Leslie B
• Lowther, W. Todd

Titel

Structural Basis for the Retroreduction of Inactivated Peroxiredoxins by Human Sulfiredoxin

Ist Teil von

• Biochemistry (Easton), 2005-06, Vol.44 (24), p.8634-8642

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Sufiredoxins (Srx) repair the inactivated forms of typical two-Cys peroxiredoxins (Prx) implicated in hydrogen peroxide-mediated cell signaling. The reduction of the cysteine sulfinic acid moiety within the active site of the Prx by Srx involves novel sulfur chemistry and the use of ATP and Mg2+. The 1.65 Å crystal structure of human Srx (hSrx) exhibits a new protein fold and a unique nucleotide binding motif containing the Gly98-Cys99-His100-Arg101 sequence at the N-terminus of an α-helix. HPLC analysis of the reaction products has confirmed that the site of ATP cleavage is between the β- and γ-phosphate groups. Cys99 and the γ-phosphate of ATP, modeled within the active site of the 2.0 Å ADP product complex structure, are adjacent to large surface depressions containing additional conserved residues. These features and the necessity for significant remodeling of the Prx structure suggest that the interactions between hSrx and typical two-Cys Prxs are specific. Moreover, the concave shape of the hSrx active site surface appears to be ideally suited to interacting with the convex surface of the toroidal Prx decamer.