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Metal Binding to Saccharomyces cerevisiae Ferrochelatase

Karlberg, Tobias LU ; Lecerof, David LU ; Gora, Monika; Silvergren, Germund; Labbe-Bois, Rosine; Hansson, Mats LU and Al-Karadaghi, Salam LU (2002) In Biochemistry 41(46). p.13499-13506
Abstract
Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into protoporphyrin IX to produce protoheme IX. The crystal structures of ferrochelatase from Saccharomyces cerevisiae in free form, in complex with Co(II), a substrate metal ion, and in complex with two inhibitors, Cd(II) and Hg(I), are presented in this work. The enzyme is a homodimer, with clear asymmetry between the monomers with regard to the porphyrin binding cleft and the mode of metal binding. The Co(II) and Cd(II) complexes reveal the metal binding site which consists of the invariant amino acids H235, E314, and S275 and solvent molecules. The shortest distance to the metal reveals that amino acid H235 is the primary... (More)
Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into protoporphyrin IX to produce protoheme IX. The crystal structures of ferrochelatase from Saccharomyces cerevisiae in free form, in complex with Co(II), a substrate metal ion, and in complex with two inhibitors, Cd(II) and Hg(I), are presented in this work. The enzyme is a homodimer, with clear asymmetry between the monomers with regard to the porphyrin binding cleft and the mode of metal binding. The Co(II) and Cd(II) complexes reveal the metal binding site which consists of the invariant amino acids H235, E314, and S275 and solvent molecules. The shortest distance to the metal reveals that amino acid H235 is the primary metal binding residue. A second site with bound Cd(II) was found close to the surface of the molecule, approximately 14 Å from H235, with E97, H317, and E326 participating in metal coordination. It is suggested that this site corresponds to the magnesium binding site in Bacillus subtilis ferrochelatase. The latter site is also located at the surface of the molecule and thought to be involved in initial metal binding and regulation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemistry
volume
41
issue
46
pages
13499 - 13506
publisher
The American Chemical Society
external identifiers
  • wos:000179236200004
  • scopus:0037137256
ISSN
0006-2960
DOI
10.1021/bi0260785
language
English
LU publication?
yes
id
8f026b07-c2f4-48bc-99b9-9033ac621d8b (old id 124804)
date added to LUP
2007-07-05 16:36:58
date last changed
2017-11-12 03:25:16
@article{8f026b07-c2f4-48bc-99b9-9033ac621d8b,
  abstract     = {Ferrochelatase is the terminal enzyme in the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into protoporphyrin IX to produce protoheme IX. The crystal structures of ferrochelatase from Saccharomyces cerevisiae in free form, in complex with Co(II), a substrate metal ion, and in complex with two inhibitors, Cd(II) and Hg(I), are presented in this work. The enzyme is a homodimer, with clear asymmetry between the monomers with regard to the porphyrin binding cleft and the mode of metal binding. The Co(II) and Cd(II) complexes reveal the metal binding site which consists of the invariant amino acids H235, E314, and S275 and solvent molecules. The shortest distance to the metal reveals that amino acid H235 is the primary metal binding residue. A second site with bound Cd(II) was found close to the surface of the molecule, approximately 14 Å from H235, with E97, H317, and E326 participating in metal coordination. It is suggested that this site corresponds to the magnesium binding site in Bacillus subtilis ferrochelatase. The latter site is also located at the surface of the molecule and thought to be involved in initial metal binding and regulation.},
  author       = {Karlberg, Tobias and Lecerof, David and Gora, Monika and Silvergren, Germund and Labbe-Bois, Rosine and Hansson, Mats and Al-Karadaghi, Salam},
  issn         = {0006-2960},
  language     = {eng},
  number       = {46},
  pages        = {13499--13506},
  publisher    = {The American Chemical Society},
  series       = {Biochemistry},
  title        = {Metal Binding to Saccharomyces cerevisiae Ferrochelatase},
  url          = {http://dx.doi.org/10.1021/bi0260785},
  volume       = {41},
  year         = {2002},
}