SIDE CHAIN INTERACTIONS GOVERNING A-HELIX STABILITY

控制 A 螺旋稳定性的侧链相互作用

• 批准号: 3279491
• 负责人: ROBERT L BALDWIN
• 金额: $ 14.98万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3279491
• 关键词: X ray crystallography; calorimetry; chemical chain length; chemical group; chemical stability; chemical structure function; circular dichroism; conformation; dipole moment; molecular site; pancreatic ribonuclease; peptide structure; protein engineering; water solution

Our aim is to detect and measure specific interactions involving side chains that affect the stability of an isolated Alpha-helix in aqueous solution. The interactions can be of two types: (1) interactions between neighboring residues, and (2) interactions between charged residues and the Alpha-helix dipole. As a starting point, the C-peptide (residues 1-13) of ribonuclease A is known to show 30% helix formation at 0 degrees C, pH 5, whereas the Zimm-Bragg equation and host-guest data predict that no 13-residue peptide can show measurable Alpha-helix formation in water, regardless of amino acid sequence or temperature. Consequently, specific side chain interactions must be important for C-peptide helix stability. Our approach is to use chemically synthesized analogs of C-peptide. We have found that two charged groups, Glu2- and His12+, at either end of the helix play a critical role in stabilizing the C-peptide helix. We have also found that Glu9 can be replaced without loss of helix stability, and therefore that a possible Glu9-...His12+ salt bridge is not important. We will use the same approach to test for a Glu2-...Arg10+ salt bridge. Tests are in progress to detect possible helix-stabilizing interactions involving Glu2-, His12+ and the Alpha-helix dipole. We will also test for neighbor-dependent interactions between side chains in pairs of specific residues.

我们的目的是检测和测量涉及侧面的特定相互作用