The crystal structures of oxidized forms of human peroxiredoxin 5 with an intramolecular disulfide bond confirm the proposed enzymatic mechanism for atypical 2-Cys peroxiredoxins.
Peroxiredoxin 5 (PRDX5) belongs to the PRDX superfamily of thiol-dependent peroxidases able to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. PRDX5 is classified in the atypical 2-Cys subfamily of PRDXs. In this subfamily, the oxidized form of the enzyme is characterized by the presence of an intramolecular disulfide bridge between the peroxidatic and the resolving cysteine residues. We report here three crystal forms in which this intramolecular disulfide bond is indeed observed. The structures are characterized by the expected local unfolding of the peroxidatic loop, but also by the unfolding of the resolving loop. A new type of interface between PRDX molecules is described. The three crystal forms were not oxidized in the same way and the influence of the oxidizing conditions is discussed.
Smeets
Aude
A
Unit of Structural Chemistry (CSTR), Université catholique de Louvain, 1, place Louis Pasteur, B-1348 Louvain-la-Neuve, Belgium.
Marchand
Cécile
C
Linard
Dominique
D
Knoops
Bernard
B
Declercq
Jean-Paul
JP
D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
D001704:Biopolymers; D004220:Disulfides; C504194:2-cys peroxiredoxin, human; C515974:PRDX5 protein, human; D054464:Peroxiredoxins