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: 3875552
• 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/3875552
• 关键词: chemical reaction; chemical structure function; circular dichroism; enzyme mechanism; enzyme structure; fluorescence spectrometry; myosins; pepsin; pepsinogens; protein biosynthesis; protein folding; protein sequence; protein structure function; stop flow technique; swine; thermodynamics; ultraviolet spectrometry; urea

This laboratory is engaged in studies on protein structure and function. Specific questions include how a protein chain, which is synthesized as a random coil can fold to a highly specific secondary and tertiary structure without aid from any external agents. The blueprint for these higher order structures must be encoded in the proteins primary sequence. This mechanism of protein folding is being investigated by studies on the behavior of swine pepsinogen, studying the kinetics of its folding and unfolding reactions and the structure of partially folded intermediates observed in these reactions. Enzymic activity in folded proteins can be modulated or even totally suppressed by covalent modifications to the proteins structure. Two examples under investigation include activation of pepsinogen to the active enzyme pepsin, by cleavage of the polypeptide chain and modulation of the various activities of myosin by phosphorylation of both its heavy and light chains by a number of kinases, which are themselves under metabolic control. The sites of these reactions and their consequences are being studied.

这个实验室从事蛋白质结构和功能的研究。 具体问题包括蛋白质链是如何合成的 随机卷曲可以折叠成高度特异的二级和三级结构 在没有任何外部代理人的帮助下。这些更高层次的蓝图 结构必须在蛋白质的初级序列中编码。这一机制 正在通过对蛋白质折叠行为的研究来研究蛋白质折叠的 猪胃蛋白酶原的折叠和解折叠动力学研究 观察到的反应和部分折叠的中间体的结构 这些反应。折叠蛋白质中的酶活性可以被调节或 甚至完全被蛋白质的共价修饰所抑制 结构。正在调查的两个例子包括激活 胃蛋白酶原通过裂解多肽而产生的活性酶 肌球蛋白的链及其磷酸化对各种活性的调节 它的重链和轻链都是由一些激酶决定的，这些激酶是 他们自己处于新陈代谢控制之下。这些反应的位置和它们的 后果正在研究中。