RULES FOR HELIX TERMINATION, THE C CAPPING BOX

螺旋终止规则，C 封盖盒

• 批准号: 6386349
• 负责人: GEORGE I MAKHATADZE
• 金额: $ 17万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6386349
• 关键词: X ray crystallography; fluorescence spectrometry; hydropathy; microcalorimetry; mutant; nuclear magnetic resonance spectroscopy; protein folding; protein sequence; protein structure; stereochemistry; structural biology; thermodynamics; ubiquitin

The long term objective of this project is to understand quantitatively the stereochemical and physico-chemical basis of alpha-helix termination. This means better understanding the mechanism of protein folding, one of the most basic problems in biomedical research. The health-related significance of this work is that the information obtained could be used for the design of new protein structures and the improvement of stabilities of biologically active proteins. The following questions will be answered: 1) Which residues in the C-capping box are important for the formation of the alphal helix termination motif? 2) What are the thermodynamic propensities of different residues at solvent exposed (C2, C1, Ccap & C ) positions of the C-capping box in an alpha-helix? 3) Do these propensities correlate with thermodynamic propensity scales obtained in other systems (alpha-helix propensities, beta-sheet propensities) or structural parameters (peptide backbone amide hydrogen exchange factors, buried and exposed surface area, etc.)? 4) What is the role of the bracketing hydrophobic interactions in formation and stabilization of the alphal motif? These questions will be answered by study of specific mutations in the C-capping box of the alpha-helix of ubiquitin using a combination of experimental methods, providing both structural (CD, fluorescence, and NMR spectroscopies and X-ray crystallography) and thermodynamic (microcalorimetry,) information on the system. From these data, we will evaluate the structural and energetic contributions of various amino acid residues at different positions of C-capping box.

这个项目的长期目标是定量地理解