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QM/MM study of the insertion of metal ion into protoporphyrin IX by ferrochelatase

Wang, Yaxue; Shen, Yong LU and Ryde, Ulf LU (2009) In Journal of Inorganic Biochemistry 103(12). p.1680-1686
Abstract
Ferrochelatase catalyzes the metallation of protoporphyrin IX in the terminal step of heme biosynthesis. Mutations in the ferrochelatase gene can lead to the disease erythropoietic porphyria. The catalyzing mechanism of ferrochelatase is still not fully understood. In this paper, we have studied the insertion of Fe2+ into the protoporphyrin IX ring by Bacillus subtilis ferrochelatase using combined quantum mechanical and molecular mechanics (QM/MM) calculations. Geometries were optimized at the BP86/6-31G* level and energies were calculated at the B3LYP/TZVP level. The overall process involves the step-wise displacement of Glu-264, His-183, and a water molecule from Fe2+, and the removal of two protons from the porphyrin ring. The... (More)
Ferrochelatase catalyzes the metallation of protoporphyrin IX in the terminal step of heme biosynthesis. Mutations in the ferrochelatase gene can lead to the disease erythropoietic porphyria. The catalyzing mechanism of ferrochelatase is still not fully understood. In this paper, we have studied the insertion of Fe2+ into the protoporphyrin IX ring by Bacillus subtilis ferrochelatase using combined quantum mechanical and molecular mechanics (QM/MM) calculations. Geometries were optimized at the BP86/6-31G* level and energies were calculated at the B3LYP/TZVP level. The overall process involves the step-wise displacement of Glu-264, His-183, and a water molecule from Fe2+, and the removal of two protons from the porphyrin ring. The rate-determining step is the cleavage of the bond between the oxygen atom of Glu-264 and Fe2+, concomitant with the formation of the first Fe-N bond. It has an energy barrier of 57 kJ mol(-1). The porphyrin ring is only slightly distorted in the enzyme active site. The residue Tyr-13 plays a key role for the catalytic process extracting two protons from protoporphyrin IX. (C) 2009 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Metallation, Fe2+, Protoporphyrin IX, Ferrochelatase, QM/MM
in
Journal of Inorganic Biochemistry
volume
103
issue
12
pages
1680 - 1686
publisher
Elsevier
external identifiers
  • wos:000271837800012
  • scopus:70350568754
ISSN
1873-3344
DOI
10.1016/j.jinorgbio.2009.09.013
language
English
LU publication?
yes
id
2d4df315-169c-4a89-9575-bf01e501303b (old id 1518810)
date added to LUP
2009-12-28 14:04:57
date last changed
2017-01-15 03:54:15
@article{2d4df315-169c-4a89-9575-bf01e501303b,
  abstract     = {Ferrochelatase catalyzes the metallation of protoporphyrin IX in the terminal step of heme biosynthesis. Mutations in the ferrochelatase gene can lead to the disease erythropoietic porphyria. The catalyzing mechanism of ferrochelatase is still not fully understood. In this paper, we have studied the insertion of Fe2+ into the protoporphyrin IX ring by Bacillus subtilis ferrochelatase using combined quantum mechanical and molecular mechanics (QM/MM) calculations. Geometries were optimized at the BP86/6-31G* level and energies were calculated at the B3LYP/TZVP level. The overall process involves the step-wise displacement of Glu-264, His-183, and a water molecule from Fe2+, and the removal of two protons from the porphyrin ring. The rate-determining step is the cleavage of the bond between the oxygen atom of Glu-264 and Fe2+, concomitant with the formation of the first Fe-N bond. It has an energy barrier of 57 kJ mol(-1). The porphyrin ring is only slightly distorted in the enzyme active site. The residue Tyr-13 plays a key role for the catalytic process extracting two protons from protoporphyrin IX. (C) 2009 Elsevier Inc. All rights reserved.},
  author       = {Wang, Yaxue and Shen, Yong and Ryde, Ulf},
  issn         = {1873-3344},
  keyword      = {Metallation,Fe2+,Protoporphyrin IX,Ferrochelatase,QM/MM},
  language     = {eng},
  number       = {12},
  pages        = {1680--1686},
  publisher    = {Elsevier},
  series       = {Journal of Inorganic Biochemistry},
  title        = {QM/MM study of the insertion of metal ion into protoporphyrin IX by ferrochelatase},
  url          = {http://dx.doi.org/10.1016/j.jinorgbio.2009.09.013},
  volume       = {103},
  year         = {2009},
}