Advanced

Structural and Mechanistic Basis of Porphyrin Metallation by Ferrochelatase

Lecerof, David LU ; Fodje, Michel LU ; Hansson, Andreas LU ; Hansson, Mats LU and Al-Karadaghi, Salam LU (2000) In Journal of Molecular Biology 297(1). p.221-232
Abstract
Ferrochelatase, the enzyme catalyzing metallation of protoporphyrin IX at the terminal step of heme biosynthesis, was co-crystallized with an isomer mixture of the potent inhibitor N-methylmesoporphyrin (N-MeMP). The X-ray structure revealed the active site of the enzyme, to which only one of the isomers was bound, and for the first time allowed characterization of the mode of porphyrin macrocycle distortion by ferrochelatase. Crystallization of ferrochelatase and N-MeMP in the presence of Cu2+ leads to metallation and demethylation of N-MeMP. A mechanism of porphyrin distortion is proposed, which assumes that the enzyme holds pyrrole rings B, C and D in a vice-like grip and forces a 36 o tilt on ring A.
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
heme synthesis, porphyrin metallation, porphyrin distortion, porphyrin demethylation, ferrochelatase
in
Journal of Molecular Biology
volume
297
issue
1
pages
221 - 232
publisher
Elsevier
external identifiers
  • scopus:0034677673
ISSN
1089-8638
DOI
10.1006/jmbi.2000.3569
language
English
LU publication?
yes
id
c5142cb7-10d6-4523-a38f-eb03c6774755 (old id 125117)
date added to LUP
2007-07-06 11:31:10
date last changed
2017-11-12 03:55:36
@article{c5142cb7-10d6-4523-a38f-eb03c6774755,
  abstract     = {Ferrochelatase, the enzyme catalyzing metallation of protoporphyrin IX at the terminal step of heme biosynthesis, was co-crystallized with an isomer mixture of the potent inhibitor N-methylmesoporphyrin (N-MeMP). The X-ray structure revealed the active site of the enzyme, to which only one of the isomers was bound, and for the first time allowed characterization of the mode of porphyrin macrocycle distortion by ferrochelatase. Crystallization of ferrochelatase and N-MeMP in the presence of Cu2+ leads to metallation and demethylation of N-MeMP. A mechanism of porphyrin distortion is proposed, which assumes that the enzyme holds pyrrole rings B, C and D in a vice-like grip and forces a 36 o tilt on ring A.},
  author       = {Lecerof, David and Fodje, Michel and Hansson, Andreas and Hansson, Mats and Al-Karadaghi, Salam},
  issn         = {1089-8638},
  keyword      = {heme synthesis,porphyrin metallation,porphyrin distortion,porphyrin demethylation,ferrochelatase},
  language     = {eng},
  number       = {1},
  pages        = {221--232},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {Structural and Mechanistic Basis of Porphyrin Metallation by Ferrochelatase},
  url          = {http://dx.doi.org/10.1006/jmbi.2000.3569},
  volume       = {297},
  year         = {2000},
}