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

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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.
Original languageUnknown
Pages (from-to)1119-1128
JournalJournal Of Biological Inorganic Chemistry
Volume14
Issue number7
Publication statusPublished - 1 Jan 2009

Cite this

@article{b061f0b449fc428dba3f39c1525caa08,
title = "Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?",
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 = "enzyme, Haem, Chelatase, residues, binding, Iron, terminal, network, murine, environment, cytochrome-c, Mutagenesis, Heme, biosynthesis, protein, metabolism, active-site, heme-biosynthesis, wild-type, ferrochelatase",
author = "Ricardo Franco",
year = "2009",
month = "1",
day = "1",
language = "Unknown",
volume = "14",
pages = "1119--1128",
journal = "Journal Of Biological Inorganic Chemistry",
issn = "0949-8257",
publisher = "Springer",
number = "7",

}

TY - JOUR

T1 - Molecular dynamics simulations of mouse ferrochelatase variants: what distorts and orientates the porphyrin?

AU - Franco, Ricardo

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - enzyme

KW - Haem

KW - Chelatase

KW - residues

KW - binding

KW - Iron

KW - terminal

KW - network

KW - murine

KW - environment

KW - cytochrome-c

KW - Mutagenesis

KW - Heme

KW - biosynthesis

KW - protein

KW - metabolism

KW - active-site

KW - heme-biosynthesis

KW - wild-type

KW - ferrochelatase

M3 - Article

VL - 14

SP - 1119

EP - 1128

JO - Journal Of Biological Inorganic Chemistry

JF - Journal Of Biological Inorganic Chemistry

SN - 0949-8257

IS - 7

ER -