Structure and function of cytochrome b561

细胞色素b561的结构和功能

• 批准号: 7393110
• 负责人: Graham A. Palmer
• 金额: $ 28.4万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-02 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393110
• 关键词: Address; Adrenal Glands; American Heart Association; Amino Acids; Antibodies; Ascorbic Acid; Bacteria; Binding; Biochemical; Biological; Biological Assay; Catecholamines; Charge; Cysteine; Cytochrome a; Cytochromes; Cytochromes b; Development; Disruption; Dopamine; Electron Transport; Electrons; Engineering; Epinephrine; Family member; Funding; Goals; Helix (Snails); Heme; Histidine; Human; Individual; Intestines; Investigation; Iron; Kinetics; Laboratories; Lanthanoid Series Elements; Lead; Ligands; Link; Measures; Membrane; Membrane Potentials; Mixed Function Oxygenases; Modeling; Molecular; Mutation; Norepinephrine; Oxidants; Oxidation-Reduction; Pathology; Pathway interactions; Phase; Physiological; Physiology; Play; Positioning Attribute; Process; Property; Protein Family; Proteins; Pulse Radiolysis; Reaction; Reagent; Recombinant Proteins; Recombinants; Reducing Agents; Regulation; Relaxation; Research Personnel; Rice; Role; Side; Signal Transduction; Structural Protein; Structure; Surface; System; Techniques; Testing; Texas; Tumor Suppression; analog; ascorbate; cytochrome b561; ear helix; falls; member; mutant; oxidation; peptide hormone; polypeptide; programs; prototype; research study; semidehydroascorbate

DESCRIPTION (provided by applicant): Adrenal ascorbate-dependent cytochrome (cyt.) b561 is a transmembrane electron transporter required for synthesis of catecholamine and some peptide hormone and is the prototype of an expanding and insufficiently characterized cyt. b561 protein family; other mammalian family members have been linked to intestinal iron transport and tumor suppression. Our overall goal is to characterize the mechanism of adrenal b561 and to use information about this cytochrome to understand the structure and function of other b561 family members. The specific aims of this project are: 1) Define the structural kernel of adrenal cyt. b561, determine its relationship to the membrane bilayer, and evaluate the kernel's generality among mammalian cyt. b561 family members; 2) Characterize the interaction of adrenal cyt. b561 with its natural reductant, ascorbate, and its natural oxidant, semidehydroascorbate; and 3) Determine the path of electron flow via adrenal cyt. b561 and its regulation. Planned experiments will be conducted on the native mammalian protein and recombinant wild type and mutant forms of the adrenal cytochrome and other mammalian cyt. b561 family members in prokaryotic and eukaryotic systems that we have developed. We will characterize the topological, structural, and kinetic properties of these recombinant proteins and purified endogenous adrenal cyt b561 using biochemical and biophysical techniques. Understanding how adrenal cyt. b561 functions is a fundamental part of understanding the physiology and pathology of epinephrine and norepinephrine and of some peptide hormones in humans. Defining similarities and differences between adrenal cyt. b561 and recently-discovered human cyt. b561 family members will accelerate characterization of the physiological and pathological roles of the newer cyt. b561s.

描述（由申请人提供）：肾上腺抗坏血酸依赖性细胞色素（Cyt。）B561是一种跨膜电子转运蛋白，用于合成儿茶酚胺和某些肽激素，并且是扩展和表征不足的cyt的原型。 B561蛋白家族；其他哺乳动物家庭成员与肠道铁运输和抑制肿瘤有关。我们的总体目标是表征肾上腺B561的机制，并使用有关该细胞色素的信息来了解其他B561家族成员的结构和功能。该项目的具体目的是：1）定义肾上腺细胞的结构核。 B561，确定其与膜双层的关系，并评估哺乳动物细胞中核的一般性。 B561家庭成员； 2）表征肾上腺细胞的相互作用。 B561及其天然还原剂，抗坏血酸及其天然氧化剂，半羟抗盐； 3）确定通过肾上腺细胞的电子流的路径。 B561及其法规。计划实验将对肾上腺细胞色素和其他哺乳动物细胞的天然哺乳动物蛋白和重组野生型和突变形式进行。 B561我们已经开发的原核生物和真核系统的家庭成员。我们将使用生物化学和生物物理技术来表征这些重组蛋白的拓扑，结构和动力学特性以及纯化的内源性肾上腺细胞Cyt B561。了解肾上腺细胞如何。 B561功能是理解肾上腺素和去甲肾上腺素的生理和病理学以及人类某些肽激素的基本组成部分。定义肾上腺细胞的相似性和差异。 B561和最近发现的人类Cyt。 B561家庭成员将加速对新Cyt的生理和病理作用的表征。 B561S。