Thermodynamic and kinetic studies of macromolec structure and enzymic mechanisms

大分子结构和酶机制的热力学和动力学研究

• 批准号: 9356061
• 负责人: Reed B. WICKNER
• 金额: $ 10.84万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9356061
• 关键词: Accounting; Affinity; Amyloid; Amyloid Fibrils; Amyloid Proteins; Binding; Biochemical Reaction; Catalysis; Circular Dichroism; Collaborations; Crowding; Dependence; Fluorescence; Goals; Investigation; Kinetics; Ligands; Measurement; Modeling; Molecular; Molecular Conformation; Nucleic Acids; Optics; Peptides; S-Adenosylhomocysteine; Secondary Protein Structure; Structure; Techniques; Thermodynamics; amyloid peptide; beta pleated sheet; biological systems; interest; intermolecular interaction; trimethyloxamine

(i) Optical studies on the structures of amyloid peptides and proteins are continuing.We are particularly interested in origin of the very intense CD spectrum which has been associated with the cross-beta structure of amyloid fibrils. This phenomenon is shown by peptides which have been shown to form amyloid with both parallel and anti-parallel beta sheet structure. (ii) In collaboration with the group of T. K. Dayie and B. Chen (Univ. of MD), we have investigated the effect of a small inert cosolute, trimethylamine oxide (TMAO), on the conformational changes of the SAM II riboswitch in the presence of increasing concentrations of the metabolite S-adenosyl-methionine (SAM) and Mg++. The free riboswitch was thought to be in an open or semi-random conformation in the absence of SAM and Mg++ and to become more folded and compact upon binding SAM and/or Mg++. Extensive measurements of the dependence of circular dichroism spectra of the riboswitch upon the concentrations of these small ligands may be quantitatively accounted for by a model, according to which SAM binds exclusively to a compact conformation. In the absence of SAM, the riboswitch seems to be a mixture of open and compact states. Low concentrations of Mg++ or TMAO bind to the open form(s), inhibiting the binding of SAM. At higher concentrations, cooperative binding of Mg++ or molecular crowding by TMAO, transform the riboswitch into the compact form, facilitating the binding of SAM. Further binding of Mg++ increases the affinity of the compact form of the riboswitch for SAM. Hydrodynamic measurements show that the riboswitch is compacted by concentrated TMAO.

(i)关于淀粉样肽和蛋白质结构的光学研究正在继续进行。我们对非常强烈的CD谱的起源特别感兴趣，这与淀粉样蛋白原纤维的交叉结构有关。这种现象可以通过多肽来证明，多肽可以形成具有平行和反平行β片结构的淀粉样蛋白。

项目成果

Effects of hydrostatic pressure on the conformational equilibrium of tryptophan synthase from Salmonella typhimurium.

• DOI: 10.1111/j.1749-6632.2009.05201.x
• 发表时间: 2010-02
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Phillips RS;Miles EW;McPhie P;Marchal S;Lange R;Holtermann G;Goody RS
• 通讯作者: Goody RS

Single-step total fractionation of single-wall carbon nanotubes by countercurrent chromatography.

• DOI: 10.1021/ac5003189
• 发表时间: 2014-04-15
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Zhang, Min;Khripin, Constantine Y.;Fagan, Jeffrey A.;McPhie, Peter;Ito, Yoichiro;Zheng, Ming
• 通讯作者: Zheng, Ming