Mechanistic studies of iron uptake into, and release from, Ferritins

Abdulqadir, Raz (2013) Mechanistic studies of iron uptake into, and release from, Ferritins. Masters thesis, University of East Anglia.

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Abstract

Abstract
Iron is the most common and perhaps the most crucial transition metal. It is essential for
virtually all of life yet it is also potentially extremely toxic; therefore, how organisms handle iron
(iron metabolism) is of critical importance. Ferritins constitute a large family of iron storage
proteins that are found throughout life, in bacteria, archaea, plants and animals. The newly
discovered ferritin from the bloom-forming pennate diatom Pseudo-nitzschia multiseries is
similar to other eukaryotic ferritins that contains a ferroxidase centre but also contains a third site
(site C) only previously found in non-heme bacterial ferritins. The mechanism of iron uptake in
P. multiseries ferritin and the effect of substitution of residues at site C has been studied using
rapid reaction kinetic methods. These revealed that oxidation in PmFTN is very rapid suggesting
a distinct mechanism of iron uptake.
Bacterioferritin (BFR) is a unique heme-containing bacterial member of the ferritin family that
stores up to 2700 iron ions as a ferric oxyhydroxide phosphate mineral within its central cavity.
This core is surrounded by 24 identical protein subunits, each of which possesses a dinuclear iron
centre that catalyses the oxidation of Fe(II) to Fe(III). The heme-binding sites are sandwiched
between pairs of subunits and coordinated by two methionine residues (one from each subunit).
The heme groups play an important role in iron release, though understanding of this has been
hampered by the difficulty in obtaining fully heme-loaded protein that is isolated from overexpressing
bacterial cultures. Here, an in vitro heme-loading method is described and used to
generate BFR containing variable amounts of heme. Studies of iron release indicate increased
heme levels only marginally increases the rate of iron release and actually lowers the extent of
iron release. These results suggest that the reconstituted heme-loaded protein behaves differently
from naturally heme-loaded protein.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Science > School of Chemistry
Depositing User:	Users 2259 not found.
Date Deposited:	05 Mar 2014 12:11
Last Modified:	05 Mar 2014 12:11
URI:	https://ueaeprints.uea.ac.uk/id/eprint/47922
DOI:

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