Structural Basis for the Retroreduction of Inactivated Peroxiredoxins by Human Sulfiredoxin
详细信息 查看全文
- 作者：Thomas J. Jö ; nsson ; Michael S. Murray ; Lynnette C. Johnson ; Leslie B. Poole ; and W. Todd Lowther
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：June 21, 2005
- 年：2005
- 卷：44
- 期：24
- 页码：8634 - 8642
- 全文大小：416K
- 年卷期：v.44,no.24(June 21, 2005)
- ISSN：1520-4995
文摘
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 moietywithin 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 nucleotidebinding motif containing the Gly98-Cys99-His100-Arg101 sequence at the N-terminus of an 
-helix.HPLC analysis of the reaction products has confirmed that the site of ATP cleavage is between the 
-and 
-phosphate groups. Cys99 and the -phosphate of ATP, modeled within the active site of the 2.0 ÅADP product complex structure, are adjacent to large surface depressions containing additional conservedresidues. These features and the necessity for significant remodeling of the Prx structure suggest that theinteractions between hSrx and typical two-Cys Prxs are specific. Moreover, the concave shape of thehSrx active site surface appears to be ideally suited to interacting with the convex surface of the toroidalPrx decamer.
-helix.HPLC analysis of the reaction products has confirmed that the site of ATP cleavage is between the -and -phosphate groups. Cys99 and the -phosphate of ATP, modeled within the active site of the 2.0 ÅADP product complex structure, are adjacent to large surface depressions containing additional conservedresidues. These features and the necessity for significant remodeling of the Prx structure suggest that theinteractions between hSrx and typical two-Cys Prxs are specific. Moreover, the concave shape of thehSrx active site surface appears to be ideally suited to interacting with the convex surface of the toroidalPrx decamer.