X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
批准号:
2198108
负责人:
EDWARD N BAKER
金额:
$6.54万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-05-01 至 1996-04-30
关键词:
X ray crystallography chemical binding chimeric proteins circular dichroism computer program /software conformation crystallization disulfide bond electron spin resonance spectroscopy glycosylation human tissue lactoferrin metal complex mutant physical model protein engineering protein sequence protein structure function receptor binding recombinant DNA recombinant proteins site directed mutagenesis transferrin ultraviolet spectrometry
中文摘要
本研究的广泛目的是双重的,(i)确定
英文摘要
The broad aims of this research are twofold, (i) to determine the
molecular basis for the biological roles of lactoferrin, the major
iron-binding protein in milk, other bodily secretions and leukocytes, and
(ii) to extend the results from the research on lactoferrin to the wider
transferrin family and to mechanisms of binding and release by binding
proteins generally.
The research will use the complementary techniques of X-ray
crystallography and site-directed mutagenesis to define the factors which
determine metal and anion binding affinity and mechanisms of binding and
release. It will have implications for understanding the control of
levels of iron and other metals in biological fluids, bodily defence
mechanisms (especially antibacterial activity), aspects of the biology of
human milk and infant health, and the bioavailability of trace elements.
The results from our previous X-ray structural studies on lactoferrin
will be used to select targets for mutagenesis, and mutant lactoferrins
will be obtained by expression of the cloned cDNA in BHK cells and
analyzed by X-ray crystallographic and solution studies. Specific aims
are:
(i) High resolution X-ray structure analyses of the recombinant N-lobe of
human lactoferrin, in both iron-bound and iron-free forms.
(ii) Investigation of metal and anion binding determinants by mutagenesis
of Asp 60, Arg 121 and the two Tyr ligands, and crystallization and
structure analysis of mutants. This will also address the control of
metal specificity and the design of metal sites in proteins generally.
(iii) Analysis of conformational change in transferrins by mutations in
the hinge region of lactoferrin. (iv) Investigation of potential receptor
binding regions by mutagenesis of specific residues.
(v) Analysis of the structural and functional effects of glycosylation of
lactoferrin by mutation of the appropriate Asn residues.
(vi) Construction of chimeric molecules using regions from lactoferrin
and transferrin, to probe structural and functional differences between
the two. The chimeric molecules will be crystallized and analyzed by
X-ray crystallography.
(vii) X-ray structure analyses of natural transferrin variants, in
particular bovine lactoferrin and the tumor-associated protein
melanotransferrin.
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会议论文
STRUCTURAL STUDIES ON MAMMALIAN AND BACTERIAL BINDING PROTEINS AND ENZYMES
-
批准号:7721740
-
项目类别:
-
资助金额:$0.36万
-
财政年份:2008
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN AND BACTERIAL BINDING PROTEINS AND ENZYMES
-
批准号:7597922
-
项目类别:
-
资助金额:$0.61万
-
财政年份:2007
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN AND BACTERIAL BINDING PROTEINS AND ENZYMES
-
批准号:7370381
-
项目类别:
-
资助金额:$0.36万
-
财政年份:2006
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN AND BACTERIAL BINDING PROTEINS AND ENZYMES
-
批准号:7180379
-
项目类别:
-
资助金额:$0.43万
-
财政年份:2005
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURE OF MAMMALIAN & BACTERIAL BINDING PROTEINS & EN
-
批准号:6976270
-
项目类别:
-
资助金额:$0.33万
-
财政年份:2004
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN BINDING PROTEINS & HEAT STABLE ENZYMES
-
批准号:6586642
-
项目类别:
-
资助金额:$14.32万
-
财政年份:2002
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN BINDING PROTEINS & HEAT STABLE ENZYMES
-
批准号:6658609
-
项目类别:
-
资助金额:$14.32万
-
财政年份:2002
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN BINDING PROTEINS & HEAT STABLE ENZYMES
-
批准号:6437560
-
项目类别:
-
资助金额:$14.32万
-
财政年份:2001
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN BINDING PROTEINS & HEAT STABLE ENZYMES
-
批准号:6119408
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1999
-
负责人:EDWARD N BAKER
-
依托单位:
STRUCTURAL STUDIES ON MAMMALIAN BINDING PROTEINS & HEAT STABLE ENZYMES
-
批准号:6250725
-
项目类别:
-
资助金额:$0.42万
-
财政年份:1997
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319301
-
项目类别:
-
资助金额:$7.25万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319299
-
项目类别:
-
资助金额:$7.0万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:6181489
-
项目类别:
-
资助金额:$9.38万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319297
-
项目类别:
-
资助金额:$7.7万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319298
-
项目类别:
-
资助金额:$7.93万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:2198109
-
项目类别:
-
资助金额:$6.38万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319295
-
项目类别:
-
资助金额:$7.11万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319300
-
项目类别:
-
资助金额:$7.12万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:2631745
-
项目类别:
-
资助金额:$8.89万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
X-RAY STRUCTURAL STUDIES OF LACTOFERRIN
-
批准号:3319296
-
项目类别:
-
资助金额:$7.9万
-
财政年份:1987
-
负责人:EDWARD N BAKER
-
依托单位:
海外基金