STRUCTURE AND REACTIVITY OF METALLOTHIONEIN
STRUCTURE AND REACTIVITY OF METALLOTHIONEIN
批准号:
3277247
负责人:
DAVID Harold PETERING
金额:
$2.77万
依托单位国家:
美国
项目类别:
财政年份:
1982
资助国家:
美国
项目状态:
已结题
起止时间:
1982-04-01 至 1986-03-31
中文摘要
该提案描述了一系列旨在阐明的调查
金属硫蛋白中多种金属离子的配位环境
并描述了它们最近被认可的化学反应性。 自从
这种富含巯基的金属结合蛋白是正常的细胞成分
在人类和几乎所有其他生物体中,并且可以由
重金属(包括镉)的管理,以及通过各种
生理应激,金属硫蛋白被认为发挥着重要作用
在锌和铜代谢、重金属解毒和
机体应激反应。 多种物理化学技术将
用于阐明详细的结构-功能关系。 我们的
主要结构工具将是 113Cd NMR,这是一种独特而强大的工具。
金属硫蛋白结构探针,最近被用来证明
镉被分组在两个离散的金属硫醇盐簇中
蛋白质。 两簇排列的通用性将通过以下方式进行测试
研究几种金属硫蛋白的 113Cd NMR 参数
来源多样。 与 13C NMR 研究相一致,配位层
镉和锌的特征将在多种条件下进行
条件。 详细的结构、动力学和热力学研究
从金属离子和脱辅基蛋白形成金属硫蛋白,
硫因,将提供对其体内可能机制的见解
装配。 金属间金属交换的动力学和机理研究
硫因结合的锌和镉,以及游离离子将被带走,
通过并行 113Cd NMR 研究不同反应性
簇与金属交换。 金属硫蛋白的新反应
包括将锌转移至脱辅基碳酸酐酶、EDTA 提取
金属离子,以及硫醇盐与DTNB的二硫键交换反应
将被重新研究以确定金属簇的关系
关于反应动力学。 具有不对称二硫醇的新型镉络合物
螯合配体将被合成作为 113NMR 研究的模型化合物。
英文摘要
This proposal describes a series of investigations designed to elucidate
the coordination environments of the multiple metal ions in metallothionein
and characterize their recently recognized chemical reactivities. Since
this sulfhydryl-rich metalbinding protein is a normal cellular constituent
in humans and virtually all other organisms and can be induced by the
administration of heavy metals, including cadmium, and by a variety of
physiological stresses, metallothionein is believed to play an important
role in zinc and copper metabolism, heavy metal detoxification, and
organismic stress response. A variety of physicochemical techniques will
be utilized to elucidate detailed structure-function relationships. Our
principal structural tool will be 113Cd NMR, which is a uniquely powerful
probe of metallothionein structure and which was recently used to prove
that cadmium is grouped in two discrete metalthiolate clusters in the
protein. The generality of the two-cluster arrangement will be tested by
investigating the 113Cd NMR parameters of metallothioneins from several
diverse sources. In concert with 13C NMR studies, the coordination spheres
of both cadmium and zinc will be characterized under a variety of
conditions. Detailed structural, kinetic and thermodynamic investigations
of the formation of metallothionein from metal ions and the apo-protein,
thionein, will provide insights into the possible mechanism of its in vivo
assembly. Kinetic and mechanistic studies of metal exchange between
thionein-bound zinc and cadmium, and the free ions will be carried out,
with parallel 113Cd NMR investigation of the differential reactivities of
the clusters to metal exchange. Novel reactions of metallothionein
including zinc transfer to apo-carbonic anhydrase, EDTA extraction of the
metal ions, and disulfide interchange reaction of the thiolates with DTNB
will be reinvestigated to determine the relationship of the metal clusters
on the reaction kinetics. Novel cadmium complexes with assymetric dithiol
chelating ligands will be synthesized as model compounds for 113NMR studies.
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Preparation and 113Cd NMR studies of homogeneous reconstituted metallothionein: reaffirmation of the two-cluster arrangement of metals.
均相重构金属硫蛋白的制备和 113Cd NMR 研究:重申金属的双簇排列。
DOI:
10.1021/bi00345a001
发表时间:
1985
期刊:
Biochemistry
影响因子:
2.9
作者:
[Otvos,JD, Engeseth,HR, Wehrli,S]
通讯作者:
Wehrli,S
Cadmium-zinc interactions in the Ehrlich cell: metallothionein and other sites.
艾利希细胞中的镉-锌相互作用:金属硫蛋白和其他位点。
DOI:
10.1007/978-3-0348-6784-9_59
发表时间:
1987
期刊:
Experientia. Supplementum
影响因子:
--
作者:
[Petering,DH, Krezoski,S, Villalobos,J, Shaw3rd,CF, Otvos,JD]
通讯作者:
Otvos,JD
DOI:
10.1021/bi00345a003
发表时间:
1985-11
期刊:
Biochemistry
影响因子:
2.9
作者:
[D. Nettesheim;H. Engeseth;J. Otvos]
通讯作者:
D. Nettesheim;H. Engeseth;J. Otvos
Interprotein metal exchange reactions of metallothionein.
金属硫蛋白的蛋白质间金属交换反应。
DOI:
10.1007/978-3-0348-6784-9_10
发表时间:
1987
期刊:
Experientia. Supplementum
影响因子:
--
作者:
[Otvos,JD, Engeseth,HR, Nettesheim,DG, Hilt,CR]
通讯作者:
Hilt,CR
Host zinc metabolism and the Ehrlich ascites tumour. Zinc redistribution during tumour-related stress.
宿主锌代谢和艾利希腹水瘤。
DOI:
10.1042/bj2330099
发表时间:
1986
期刊:
The Biochemical journal
影响因子:
--
作者:
[Ujjani,B, Krakower,G, Bachowski,G, Krezoski,S, Shaw3rd,CF, Petering,DH]
通讯作者:
Petering,DH
共 7 条
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批准号:8769739
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资助金额:$21.85万
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财政年份:2014
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Biology-Environmental Health Science Nexus: Inquiry, Content, and Communication
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资助金额:$19.04万
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财政年份:2009
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Administrative Core
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财政年份:2009
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依托单位:
Biology-Environmental Health Science Nexus: Inquiry, Content, and Communication
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资助金额:$26.73万
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财政年份:2009
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Biology-Environmental Health Science Nexus: Inquiry, Content, and Communication
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资助金额:$26.58万
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财政年份:2009
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依托单位:
Community Outreach and Education Core
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批准号:7618059
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资助金额:$15.74万
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财政年份:2009
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负责人:DAVID Harold PETERING
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依托单位:
Pilot Project Program
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批准号:7618058
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项目类别:
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资助金额:$13.24万
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财政年份:2009
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负责人:DAVID Harold PETERING
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依托单位:
Integrative Health Sciences Core
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批准号:7618056
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资助金额:$42.55万
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财政年份:2009
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负责人:DAVID Harold PETERING
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依托单位:
Biology-Environmental Health Science Nexus: Inquiry, Content, and Communication
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项目类别:
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资助金额:$27.0万
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财政年份:2009
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依托单位:
Facility/Service Cores
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资助金额:$31.67万
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资助金额:$13.17万
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NIEHS Center Aquatic Animal Facility Renovation
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资助金额:$43.02万
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财政年份:2009
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负责人:DAVID Harold PETERING
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依托单位:
Fluorescent Cellular Zinc Sensors. What Are They Imaging?
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批准号:7671355
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资助金额:$28.42万
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财政年份:2008
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依托单位:
Fluorescent Cellular Zinc Sensors. What Are They Imaging?
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资助金额:$27.85万
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财政年份:2008
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依托单位:
Fluorescent Cellular Zinc Sensors. What Are They Imaging?
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资助金额:$28.13万
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财政年份:2008
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依托单位:
Fluorescent Cellular Zinc Sensors. What Are They Imaging?
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批准号:7506699
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项目类别:
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资助金额:$26.22万
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财政年份:2008
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负责人:DAVID Harold PETERING
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依托单位:
Aquatic Animal Facilities
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批准号:7514768
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项目类别:
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资助金额:$15.41万
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财政年份:2007
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负责人:DAVID Harold PETERING
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依托单位:
Administrative Core
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批准号:7514760
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项目类别:
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资助金额:$12.97万
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财政年份:2007
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FISH CONSUMPTION RISK COMMUNICATION IN ETHNIC MILWAUKEE
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