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JBIC Journal of Biological Inorganic Chemistry

, Volume 14, Issue 7, pp 1119–1128 | Cite as

Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?

  • Borys Szefczyk
  • M. Natália D. S. Cordeiro
  • Ricardo Franco
  • José A. N. F. Gomes
Original Paper

Abstract

Molecular dynamics simulations of the wild-type and variant forms of the mouse ferrochelatase in complex with the product (haem) have been performed using the GROMOS96 force field, in the NpT ensemble. Ferrochelatase, the last enzyme in the catalytic pathway of the haem biosynthesis, catalyses the reaction of insertion of a ferrous ion into protoporphyrin IX by distorting the planar geometry of the latter reactant. The simulations presented aim at understanding the role of active-site residues in this catalytic process. Analysis of the simulation trajectories explains the consequences of the mutations introduced and sheds more light on the role of the His209 residue in porphyrin macrocycle distortion. The function of residues coordinating propionate groups of the haem molecule is discussed in terms of stability of the substrate and product complexes.

Keywords

Haem Heme biosynthesis Chelatase Mutagenesis Iron metabolism 

Notes

Acknowledgments

Calculations were carried out at the Wrocław Centre for Networking and Supercomputing. B.S. would like to thank the Fundação para a Ciência e a Tecnologia (Lisbon) for fellowship no. SFRH/BPD/38809/2007. Also, B.S. would like to thank Edyta Dyguda-Kazimierowicz for expertise on homology modelling and Miguel Jorge for useful discussions about MD simulations.

Supplementary material

775_2009_556_MOESM1_ESM.pdf (985 kb)
PDF (984 KB)

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Copyright information

© SBIC 2009

Authors and Affiliations

  • Borys Szefczyk
    • 1
    • 2
  • M. Natália D. S. Cordeiro
    • 1
  • Ricardo Franco
    • 3
  • José A. N. F. Gomes
    • 1
  1. 1.REQUIMTE, Department of Chemistry, Faculty of ScienceUniversity of PortoPortoPortugal
  2. 2.Institute of Physical and Theoretical ChemistryWrocław University of TechnologyWrocławPoland
  3. 3.REQUIMTE, Department of Chemistry, Faculty of Science and TechnologyNew University of LisbonCaparicaPortugal

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