PMID- 10535922
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 22
DP  - 1999 Oct 26
TI  - Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein
      23 kDa/proliferation-associated gene product.
PG  - 12333-8
AB  - Heme-binding protein 23 kDa (HBP23), a rat isoform of human
      proliferation-associated gene product (PAG), is a member of the peroxiredoxin
      family of peroxidases, having two conserved cysteine residues. Recent biochemical
      studies have shown that HBP23/PAG is an oxidative stress-induced and
      proliferation-coupled multifunctional protein that exhibits specific bindings to 
      c-Abl protein tyrosine kinase and heme, as well as a peroxidase activity. A 2.6-A
      resolution crystal structure of rat HBP23 in oxidized form revealed an unusual
      dimer structure in which the active residue Cys-52 forms a disulfide bond with
      conserved Cys-173 from another subunit by C-terminal tail swapping. The active
      site is largely hydrophobic with partially exposed Cys-173, suggesting a
      reduction mechanism of oxidized HBP23 by thioredoxin. Thus, the unusual cysteine 
      disulfide bond is involved in peroxidation catalysis by using thioredoxin as the 
      source of reducing equivalents. The structure also provides a clue to possible
      interaction surfaces for c-Abl and heme. Several significant structural
      differences have been found from a 1-Cys peroxiredoxin, ORF6, which lacks the
      C-terminal conserved cysteine corresponding to Cys-173 of HBP23.
FAU - Hirotsu, S
AU  - Hirotsu S
AD  - Department of Molecular Biology, Nara Institute of Science and Technology, 8916-5
      Takayama, Ikoma, Nara 630-0101, Japan.
FAU - Abe, Y
AU  - Abe Y
FAU - Okada, K
AU  - Okada K
FAU - Nagahara, N
AU  - Nagahara N
FAU - Hori, H
AU  - Hori H
FAU - Nishino, T
AU  - Nishino T
FAU - Hakoshima, T
AU  - Hakoshima T
LA  - eng
SI  - PDB/1QQ2
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 42VZT0U6YR (Heme)
RN  - EC 1.11.1.- (Peroxidases)
RN  - EC 1.11.1.15 (BAS1 protein, Arabidopsis)
RN  - EC 1.11.1.15 (Peroxiredoxins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arabidopsis Proteins
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Heme/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peroxidases/*chemistry/metabolism
MH  - Peroxiredoxins
MH  - Protein Conformation
MH  - Rats
MH  - Recombinant Proteins/chemistry
MH  - Sequence Homology, Amino Acid
PMC - PMC22917
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1073/pnas.96.22.12333 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12333-8. doi:
      10.1073/pnas.96.22.12333.