THERMODYNAMIC AND KINETIC STUDIES OF PROTEIN STRUCTURE AND ENZYME MECHANISMS

蛋白质结构和酶机制的热力学和动力学研究

• 批准号: 3964027
• 负责人: P MCPHIE
• 金额: --
• 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/3964027
• 关键词: acidity /alkalinity; chelation therapy; chemical cleavage; chemical structure function; circular dichroism; conformation; drug design /synthesis /production; enzyme induction /repression; enzyme structure; pepsin; pepsinogens; stop flow technique; ultraviolet spectrometry; zymogens

On Exposure to acid pH, swine pepsinogen undergoes self cleavage to produce psuedo pepsin, by the loss of the first 16 residues in its sequence. Returning to neutrality, produces an irreversible conformational change in psuedo pepsin to a new globular form, which seems to be identical to the rapidly formed transient intermediate previously detected during the folding of intact pepsinogen. Like pepsinogen, but unlike native psuedo pepsin, this neutral pH form of the protein can be reversibly unfolded by urea or high pH. The mechanism of the folding reaction, the structure and stability of this neutral pH form of psuedo pepsin and the role of the first 16 residues in the mechanism of folding of pepsinogen are all under investigation.

在暴露于酸性pH时，猪胃蛋白酶原经历自我切割以产生 假胃蛋白酶，通过其序列中前16个残基的丢失。 恢复中性，产生不可逆转的构象变化， psuedo胃蛋白酶的一个新的球状形式，这似乎是相同的， 快速形成的瞬态中间体，之前在 完整胃蛋白酶原的折叠。 类似胃蛋白酶原，但不同于天然假 胃蛋白酶，这种中性pH形式的蛋白质可以可逆地解折叠， 折叠反应的机理，结构和 这种中性pH形式的假胃蛋白酶的稳定性和 胃蛋白酶原折叠机制中的前16个残基都在 调查