CRYSTALLOGRAPHIC STUDIES OF PROTEIN STRUCTURE/FUNCTION

这个应用程序的长期目标是理解结构 酶的催化能力的起源，以了解功能 蛋白质构象变化和原子波动的重要性 表征蛋白质中辐射损伤的结构后果 和核酸，并应用蛋白质结晶学技术 和计算机建模，以提供详细的分子图像 细菌趋化感觉系统。第一个目标应该是 为酶制剂的合理设计提供重要的基础信息 药物和对几种疾病的了解，如肺气肿， 涉及酶缺乏或一种酶是严重有毒的 实质性的。对蛋白质结构变化的认识 既响应于特定配体的结合，又作为 常温下可利用的动能将是互补的。 静态蛋白质的结构图。辐射损害对 活体是一个重要的健康考虑因素，而准确的 受损分子的结构细节往往是不确定的。 受损蛋白质和核仁的结构表征 酸应该有助于防辐射化合物的设计，而且 对于那些考虑将辐射用作食物的人来说可能是有用的 防腐措施。细菌趋化系统是一种很有潜力的 人类感觉系统的模型，如嗅觉、味觉和 可能是触摸。我们的具体目标包括决心 嗜热脂肪芽孢杆菌丙氨酸消旋酶的三维结构 单晶X射线法的2.5A或更高分辨率 衍射法测定这一络合物的结构 底物D-丙氨酸或L-丙氨酸与磷酸盐慢结合的酶 缓蚀剂的结晶和晶体结构的测定 鼠伤寒沙门氏菌趋化系统的甲酯酶； 在高分辨率(即约1.5A)下测定和细化 弹性酶与底物在其酰基酶中络合的晶体结构 中间体、酶产物形式和米氏复合体 低温X射线酰化前底物酶 结晶学.抹香鲸结构的表征 50%辐射损伤的MET-肌红蛋白；几种类DNA的特征 相同剂量的寡核苷酸双链分子，以及完整的 两种蛋白质的压力和温度依赖性的测定 结构。

The long-term goals of this application are to understand the structural origins of the catalytic power of enzymes, to understand the functional importance of protein conformational changes and atomic fluctuations, to characterize the structural consequences of radiation damage in proteins and nucleic acids, and to apply the techniques of protein crystallography and computer modelling to provide a detailed molecular picture of the bacterial chemotactic sensory system. The first of these aims should provide basic information important to rational design of enzyme-active drugs and to an understanding of several diseases, such as emphysema, that involve enzyme deficiency or where an enzyme is the critical toxic substance. Knowledge of the changes in structure that proteins undergo both in response to the binding of specific ligands and as a consequence of the kinetic energy available at ordinary temperatures will be complementary to the structural picture of the static protein. Radiation damage to living organisms is a significant health consideration, and the precise details of the structures of the damaged molecules are often uncertain. Characterization of the structures of the damaged proteins and nucleic acids should aid in the design of radiation-protecting compounds, and also may be of use for people who consider the use of radiation as a food preservative measure. The bacterial chemotactic system is a good potential model for the sensory systems in human beings, such as smell, taste and possibly touch. Our specific aims include the determination of the three-dimensional structure of B. stearothermophilus alanine racemase at 2.5A resolution or higher by the method of single-crystal X-ray diffraction, the determination of the structures of the complex of this enzyme with substrate D- or L- alanine and with a phosphonate slow-binding inhibitor; the crystallization and crystal structure determination of the methyl esterase from the chemotactic system of Salmonella typhimurium; the determination and refinement at high resolution (i.e., about 1.5A) of the crystal structures of elastase complexed with substrate in its acyl-enzyme intermediate form, the enzyme-product form, and the Michaelis complex of enzyme with substrate prior to acylation by low-temperature X-ray crystallography; characterization of the structure of sperm-whale met-myoglobin at 50% radiation damage; characterization of several DNA-like oligonucleotide duplex molecules at similar doses, and the complete determination of the pressure and temperature dependence of two protein structures.