RESEARCH INTERESTS
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My research interests are in the general area of iron protein biochemistry. The goal is to elucidate the structure-function relationships and better understand the role of these crucial proteins in the regulation of cellular iron homeostasis. Proteins such as human transferrin, cytoplasmic and mitochondrial ferritins of different origins, human and bacterial frataxin are being investigated. The hope is to generate new knowledge that is essential for the rational development of new treatments for iron overload diseases and other defects in iron metabolism. Iron is a vital element for almost all living organisms due to its essential role in numerous metabolic processes. However, excess free iron has been implicated in neurodegenerative diseases, apoptosis, and also in the generation of harmful free radicals that cause damage to membranes, proteins and nucleic acids. The low solubility of iron at physiological conditions (~ 10-18 M) has compelled living organisms to adapt efficient iron transport and storage mechanisms, one of which is transferrin, a plasma transport protein which carries iron in the circulation from the gut to the bone marrow and other tissues for the synthesis of hemoglobin and other iron containing proteins.
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The iron-transport protein "Transferrin" Transferrin
is a naturally occurring metal chelating protein that is responsible
for the transport and donation of Fe to
cells and
tissues where it is utilized by many iron-containing enzymes. It is a bilobale protein (C- and N-lobes)
with two high affinity Fe(III) binding sites. In
each lobe
iron is bound to two
tyrosines, one aspartate, one histidine and a bidentate synergistic
carbonate
anion. The iron
loaded transferrin (holotransferrin)
delivers its content of iron by endocytosis after interaction with the
transferrin receptor on the cell membrane. Holotransferrin
has a high
affinity for its receptor while Fe-free transferrin
does not, and this has important physiological implications in terms of
the
mechanism of transferrin uptake by cells
By
binding iron tightly, transferrin helps to avoid
the formation of free radicals reactions catalyzed by iron. These
reactions are implicated in the formation of various cancers,
arteriosclerosis,
arthritis, and liver and heart diseases. Transferrin is also the
target
of chelation therapy used to treat individuals with diseases of iron
overload
such as “Thalassemia” and “Hemochromatosis”,
the most common
genetic disorder in this country, affecting 1 out of 200
individuals. |
 Receptor
Transferrin Endocytosis
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