Protein Allostery and Catalysis Beyond Bragg Diffraction

布拉格衍射之外的蛋白质变构和催化

• 批准号: 10250499
• 负责人: Nozomi Ando
• 金额: $ 38.66万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10250499
• 关键词: Biochemistry; Catalysis; Chemistry; Crystallization; Drug Targeting; Enzymatic Biochemistry; Enzymes; Methods; Molecular; Motion; Multienzyme Complexes; Natural Products; Pharmacologic Substance; Physical Chemistry; Play; Proteins; Reaction; Regulation; Roentgen Rays; Role; Structural Protein; Structure; flexibility; frontier; interest; public health relevance; structural biology

Abstract What are the structural dynamics involved in protein allostery and catalysis? How do flexible enzymes perform challenging chemistry? Can we animate crystal structures of proteins? These are outstanding questions in bi- ology, which motivate studies of proteins in motion. Capturing proteins in action is the next frontier of structural enzymology. By working at the interface of biochemistry and physical chemistry, we aim to go beyond the stat- ic picture of enzymes that is obtained by traditional Bragg diffraction and instead recover dynamic information with non-conventional X-ray scattering and diffraction approaches. We are particularly interested in enzymes of biomedical importance that have been challenging to study by traditional methods, such as drug targets that are allosterically regulated and enzymes that complex mechanisms to synthesize natural products with phar- maceutical potential.

抽象的 蛋白质变构和催化中涉及哪些结构动力学？柔性酶如何表现 具有挑战性的化学？我们可以使蛋白质的晶体结构动画吗？这些是双方的杰出问题 OLOGO，激励对运动中的蛋白质进行研究。在作用中捕获蛋白质是结构的下一个领域 酶学。通过在生物化学和物理化学的界面工作，我们的目标是超越统计 通过传统的布拉格衍射获得的酶的IC图片，而是恢复动态信息 具有非规定的X射线散射和衍射方法。我们对 生物医学重要性是通过传统方法进行研究的具有挑战性的，例如药物靶标的 是由变构调节和酶，使其复杂的机制使天然产物与Phar-合成天然产物 Maceutical潜力。