Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product

• DOI: 10.1073/pnas.96.22.12333
• Publication Date: 2002-07-26T14:38:21Z
• Authors: Shoko Hirotsu; Yasuko Abe; Kengo Okada; Noriyuki Nagahara; Hiroyuki Hori; Takeshi Nishino; Toshio Hakoshima
• Keywords: Peroxiredoxin; Conserved sequence; Hemeprotein

Heme-binding protein 23 kDa (HBP23), a rat isoform of human proliferation-associated gene product (PAG), is member the peroxiredoxin family peroxidases, having two conserved cysteine residues. Recent biochemical studies have shown that HBP23/PAG an oxidative stress-induced and proliferation-coupled multifunctional exhibits specific bindings to c-Abl tyrosine kinase heme, as well peroxidase activity. A 2.6-A resolution crystal structure HBP23 in oxidized form revealed unusual dimer which active residue Cys-52 forms disulfide bond with Cys-173 from another subunit by C-terminal tail swapping. The site largely hydrophobic partially exposed Cys-173, suggesting reduction mechanism thioredoxin. Thus, involved peroxidation catalysis using thioredoxin source reducing equivalents. also provides clue possible interaction surfaces for heme. Several significant structural differences been found 1-Cys peroxiredoxin, ORF6, lacks corresponding HBP23.