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.

摘要 蛋白质变构和催化的结构动力学是什么？柔性酶如何发挥作用 挑战化学？我们能让蛋白质的晶体结构动起来吗？这些都是双边关系中悬而未决的问题。 学，它激发了对运动蛋白质的研究。捕捉蛋白质的活动是结构科学的下一个前沿领域， 酶学通过在生物化学和物理化学的接口工作，我们的目标是超越统计- 通过传统布拉格衍射获得的酶的ic图像，而是恢复动态信息 用非传统的X射线散射和衍射方法。我们特别感兴趣的是 生物医学的重要性，一直具有挑战性的研究，通过传统的方法，如药物靶点， 是变构调节和酶，复杂的机制，合成天然产物与phar- 潜力巨大。