MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
批准号:
2139591
负责人:
WESLEY R HARRIS
金额:
$13.09万
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-08-06 至 1997-04-30
中文摘要
血清转铁蛋白是负责铁离子运输的蛋白质
英文摘要
Serum Transferrin is the protein responsible for the transport of Fe3+
between sites of uptake, utilization, and storage. It also binds Ca3+,
In3+, and Al3+ when these metal ions enter the blood. Characterization
of the interactions of these metal ions with transferrin is important for
understanding the mechanism of intracellular iron release, for the
development of new drugs for treating iron overload, and for
understanding the pharmacology and toxicology of compounds of the group
13 metal ions.
Based on previous results from this project, it is proposed that iron
removal proceeds through two parallel pathways, one which appears to be
limited by a conformational change in the protein, and a second pathway
which is first-order in ligand. The proposed research will further
evaluate this mechanism versus alternative proposals from other labs.
Rates of metal ion removal for Fe3+, Al3+, Ga3+, and In3+ will be
followed using electronic spectroscopy and electrophoresis to determine
the effect of the metal ion on absolute rates of exchange and on the
relative importance of the two pathways. Detailed comparisons between
neutral and anionic ligands will be made to assess the role of anionic
ligands as allosteric modifiers of transferrin. The effects of inorganic
salts on the two pathways for iron removal will be measured, and
anion-induced conformational changes in transferrin will be characterized
by circularly polarized luminescence of lanthanide-Tf complexes.
Additional studies of anion and metal binding to apotransferrin at the
low pH associated with intracellular iron release will be conducted to
determine whether anions can promote iron release by thermodynamic
competition for a common binding site.
It is proposed that cationic amino acid side chains near the
metal-binding site may be the locus for selective anion effects on the
kinetics of iron removal. Recombinant transferrins will be prepared in
which residues suspected to be involved in anion binding will be
selectively altered. The thermodynamics of anion binding to the
recombinant proteins will be measured to determine the residues involved
in anion binding, and the kinetics of iron release from the recombinant
proteins to a series of neutral and anionic ligands will be evaluated.
In addition, the effect of ligands and non-coordinating anions on the
rate of exchange of the synergistic bicarbonate anion in Fe-HCO3-Tf will
be followed by a new technique involving mass spectral detection of [13C)
CO2.
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会议论文
ACCELERATING IRON CHELATION FROM SERUM TRANSFERRIN
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批准号:6764096
-
项目类别:
-
资助金额:$23.16万
-
财政年份:2000
-
负责人:WESLEY R HARRIS
-
依托单位:
ACCELERATING IRON CHELATION FROM SERUM TRANSFERRIN
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批准号:6537932
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项目类别:
-
资助金额:$23.43万
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财政年份:2000
-
负责人:WESLEY R HARRIS
-
依托单位:
ACCELERATING IRON CHELATION FROM SERUM TRANSFERRIN
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批准号:6638723
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项目类别:
-
资助金额:$23.3万
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财政年份:2000
-
负责人:WESLEY R HARRIS
-
依托单位:
ACCELERATING IRON CHELATION FROM SERUM TRANSFERRIN
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批准号:6090868
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项目类别:
-
资助金额:$23.82万
-
财政年份:2000
-
负责人:WESLEY R HARRIS
-
依托单位:
ACCELERATING IRON CHELATION FROM SERUM TRANSFERRIN
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批准号:6390952
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项目类别:
-
资助金额:$23.55万
-
财政年份:2000
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
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批准号:2139590
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项目类别:
-
资助金额:$0.56万
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财政年份:1984
-
负责人:WESLEY R HARRIS
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依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN BY AMINOPHOSP
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批准号:3446175
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项目类别:
-
资助金额:$5.0万
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财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
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批准号:3233851
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项目类别:
-
资助金额:$12.94万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
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批准号:3233852
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项目类别:
-
资助金额:$5.33万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
-
批准号:2139589
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项目类别:
-
资助金额:$13.09万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
-
批准号:3233853
-
项目类别:
-
资助金额:$5.16万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
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批准号:2139592
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项目类别:
-
资助金额:$13.55万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
-
批准号:3233854
-
项目类别:
-
资助金额:$5.41万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN BY AMINOPHOSP
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批准号:3447362
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项目类别:
-
资助金额:$5.28万
-
财政年份:1984
-
负责人:WESLEY R HARRIS
-
依托单位:
MECHANISM OF IRON REMOVAL FROM TRANSFERRIN
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批准号:3233848
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项目类别:
-
资助金额:$1.57万
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财政年份:1984
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负责人:WESLEY R HARRIS
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依托单位:
海外基金