Metal binding sites of human H-chain ferritin and iron transport mechanism to the ferroxidase sites: A molecular dynamics simulation study
Article first published online: 1 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 81, Issue 6, pages 1042–1050, June 2013
How to Cite
Laghaei, R., Evans, D. G. and Coalson, R. D. (2013), Metal binding sites of human H-chain ferritin and iron transport mechanism to the ferroxidase sites: A molecular dynamics simulation study. Proteins, 81: 1042–1050. doi: 10.1002/prot.24251
- Issue published online: 22 MAY 2013
- Article first published online: 1 APR 2013
- Accepted manuscript online: 23 JAN 2013 12:40PM EST
- Manuscript Accepted: 18 DEC 2012
- Manuscript Revised: 29 NOV 2012
- Manuscript Received: 3 OCT 2012
- National Science Foundation. Grant Number: CHE-0750332.
- three-fold channel;
- four-fold channel;
- ion channels;
- all atom MD;
- catalytic site
We study via all atom classical molecular dynamics (MD) simulation the process of uptake of ferrous ions (Fe2+) into the human ferritin protein and the catalytic ferroxidase sites via pores (“channels”) in the interior of the protein. We observe that the three-fold hydrophilic channels serve as the main entrance pathway for the Fe2+ ions. The binding sites along the ion pathway are investigated. Two strong binding sites, at the Asp131 and Glu134 residues and two weak binding sites, at the His118 and Cys130 are observed inside the three-fold channel. We also identify an explicit pathway for an ion exiting the channel into the central core of the protein as it moves to the ferroxidase site. The diffusion of an Fe2+ ion from the inner opening of the channel to a ferroxidase site located in the interior region of the protein coat is assisted by Thr135, His136 and Tyr137. The Fe2+ ion binds preferentially to site A of the ferroxidase site. © 2013 Wiley Periodicals, Inc.