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

• Published in: Journal of biological inorganic chemistry Vol. 14; no. 7; pp. 1119 - 1128
• Main Authors: Szefczyk, Borys, Cordeiro, M. Natália D. S, Franco, Ricardo, Gomes, José A. N. F
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.09.2009; Springer-Verlag
• Subjects: Amino Acid Sequence; Animals; Biocatalysis; Biochemistry; Biomedical and Life Sciences; Catalytic Domain; Computational Biology - methods; Computer Simulation; Crystallography, X-Ray; Ferrochelatase - chemistry; Ferrochelatase - genetics; Iron - metabolism; Life Sciences; Mice; Microbiology; Models, Molecular; Molecular Conformation; Molecular Sequence Data; Mutant Proteins - chemistry; Original Paper; Porphyrins - chemistry; Protein Binding; Protein Interaction Domains and Motifs; Sequence Alignment; Iron metabolism; Haem; Heme biosynthesis; Mutagenesis; Chelatase
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-009-0556-y

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.