Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State.

Autor: Forshaw TE; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Reisz JA; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Nelson KJ; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Gumpena R; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Lawson JR; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Jönsson TJ; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Wu H; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Clodfelter JE; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Johnson LC; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Furdui CM; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.; Center for Redox Biology and Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.; Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA., Lowther WT; Center for Structural Biology, Department of Biochemistry, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.; Center for Redox Biology and Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.; Comprehensive Cancer Center, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Jazyk: angličtina
Zdroj: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2021 Jun 11; Vol. 10 (6). Date of Electronic Publication: 2021 Jun 11.
DOI: 10.3390/antiox10060946
Abstrakt: Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H 2 O 2 ), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO 2 H) favoring the multimeric structure of the reduced enzyme. Here, we present a study on the structural requirements for the repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx) and the relative efficacy of physiological reductants hydrogen sulfide (H 2 S) and glutathione (GSH) in this reaction. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. The loss of this interface within engineered Prx2 and Prx3 dimers yielded variants more resistant to hyperoxidation and repair by Srx. Finally, we reveal for the first time Prx isoform-dependent use of and potential cooperation between GSH and H 2 S in supporting Srx activity.
Databáze: MEDLINE
Externí odkaz: