MOSSBAUER STUDIES OF HEME MODELS AND MUTANT MYOGLOBINS
血红素模型和突变肌红蛋白的穆斯鲍尔研究
基本信息
- 批准号:3307971
- 负责人:
- 金额:$ 11.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-09-30 至 1995-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In studying structure-function relationships of iron proteins,
spectroscopic techniques like EPR and Mossbauer have proved invaluable for
understanding the chemical nature of the active center. The spectroscopic
parameters provide a clear way of comparing one iron protein with others
having different catalytic properties. The proposed project involves the
physical characterization of heme model compounds and mutant forms of
myoglobin. We are interested in heme model compounds having a) pi-cation
radicals, b) a ferric "mixed-spin" iron state, or c) a low-spin ferric iron
with an unusual dxy ground state. The cation radicals are models for
intermediate states in the catalytic cycles of many mammalian heme enzymes,
such as the peroxidases. Our studies on heme models will be done in
collaboration with Dr. W. R. Scheidt. We hope to clarify how the
peripheral constituents and axial ligands of the heme influence 1) the
ground spin state of the iron, 2) the orbital occupied by the cation
radical, and 3) the magnetic coupling between the iron and the radical. We
will specifically use Mossbauer and EPR spectroscopy to study heme
compounds related to the octaethyl porphyrin (OEP) model
[Fe(OEP')C1]2(SbC16)2 and the equivalent compound having one more electron
and a single counterion. The spectroscopic and magnetic parameters of the
models will be determined by computer simulation, and will be correlated
with structural information from x-ray diffraction measurements. The case
for an iron protein being in the "mixed spin" state was first convincingly
made for ferricytochrome c'. Since then, many other enzymes and model
compounds have exhibited this state. We would like to clarify the chemical
conditions necessary to stabilize this state. The low-spin ferric heme
models of interest are those related to the tetraphenyl porphyrin (TPP)
model [Fe(TPP)(CNBu)2]+ which, unlike nearly any other low-spin ferric
system, has an axial low=spin EPR spectrum and may have its unpaired
electron in a dxy orbital. We hope to elucidate the bonding properties
required of the axial ligands in order to produce this unusual state.
The myoglobin studies will be done in collaboration with Dr. S. G. Sligar,
and will focus on clarifying how the properties of the iron ligand binding
site are perturbed by modifications of the polypeptide backbone.
Recombinant techniques will be used to generate mutations of the E and F
chains. The mutant myoglobins will be investigated by looking at the
binding properties of CO and O2 relative to the wild type, and by Mossbauer
spectroscopy and EPR. The Mossbauer parameters will be analyzed in a
crystal field model, which should afford insight into how crystal field
potentials correlate with small structural changes in a protein, and how
those structural changes in turn influence the reactivity of the heme
binding site. To facilitate the analysis of the Mossbauer data on all of
these systems, we will develop an iterative multiparameter computer fitting
program based on modern minimization algorithms.
在研究铁蛋白的结构-功能关系时,
光谱技术,如EPR和穆斯堡尔谱已被证明是非常宝贵的,
了解活性中心的化学性质。 光谱
参数提供了一个明确的方式比较一个铁蛋白与其他
具有不同的催化性能。 拟议项目涉及
血红素模型化合物的物理表征和
肌红蛋白 我们感兴趣的血红素模型化合物具有a)π-阳离子
自由基,B)三价铁“混合自旋”铁态,或c)低自旋三价铁
具有不寻常的dxy基态。 阳离子自由基是
许多哺乳动物血红素酶催化循环的中间状态,
如过氧化物酶。 我们对血红素模型的研究将在
与W博士合作R.沙伊特 我们希望澄清,
外周成分和轴向配体的血红素影响1)
铁的基态自旋,2)阳离子占据的轨道
自由基,和3)铁和自由基之间的磁耦合。 我们
将专门使用穆斯堡尔和EPR光谱学来研究血红素
八乙基卟啉(OEP)模型相关化合物
[Fe(OEP ′)C1]2(SbC 16)2和多一个电子的等效化合物
和一个国家。 的光谱和磁性参数
模型将通过计算机模拟确定,并将与
具有来自X射线衍射测量的结构信息。 的情况
铁蛋白质处于“混合自旋”状态,
专为铁细胞色素C制造。 从那时起,许多其他酶和模型
化合物表现出这种状态。 我们想澄清一下
这是稳定这种状态的必要条件。 低自旋铁血红素
感兴趣的模型是那些与四苯基卟啉(TPP)有关的模型。
模型[Fe(TPP)(CNBu)2]+,与几乎任何其他低自旋铁
系统,具有轴向低自旋EPR谱,并且可能具有其不成对的
dxy轨道上的电子。 我们希望能阐明
为了产生这种不寻常的状态,需要轴向配体。
肌红蛋白研究将与S. G.斯利加,
并将重点阐明铁配体结合的性质
位点被多肽骨架的修饰扰乱。
重组技术将用于产生E和F的突变,
店 突变的肌红蛋白将通过观察
CO和O2相对于野生型的结合特性,并通过穆斯堡尔谱
光谱学和EPR。 穆斯堡尔参数将在一个
晶体场模型,这应该提供洞察如何晶体场
电位与蛋白质中的小结构变化相关,以及如何
这些结构变化反过来又影响血红素的反应性
结合位点 为了便于分析所有的穆斯堡尔数据,
这些系统,我们将开发一个迭代多参数计算机拟合
基于现代最小化算法的程序。
项目成果
期刊论文数量(0)
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{{ truncateString('CHARLES E SCHULZ', 18)}}的其他基金
MOSSBAUER STUDIES OF HEME MODELS AND MUTANT MYOGLOBINS
血红素模型和突变肌红蛋白的穆斯鲍尔研究
- 批准号:
2185981 - 财政年份:1992
- 资助金额:
$ 11.06万 - 项目类别:
MOSSBAUER STUDIES OF HEME MODELS AND MUTANT MYOGLOBINS
血红素模型和突变肌红蛋白的穆斯鲍尔研究
- 批准号:
2185980 - 财政年份:1992
- 资助金额:
$ 11.06万 - 项目类别:
MOSSBAUER STUDIES OF LOW-SPIN FERRIC PROTEINS
低自旋三价铁蛋白的莫斯鲍尔研究
- 批准号:
3438502 - 财政年份:1987
- 资助金额:
$ 11.06万 - 项目类别:
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