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 蛋白质变构和催化涉及哪些结构动力学？柔性酶如何发挥作用 具有挑战性的化学？我们可以动画化蛋白质的晶体结构吗？这些是双方面的突出问题 学，它激发了对运动蛋白质的研究。捕获活动中的蛋白质是结构研究的下一个前沿领域 酶学。通过研究生物化学和物理化学的交叉点，我们的目标是超越统计 通过传统布拉格衍射获得的酶的图像，并恢复动态信息 采用非常规 X 射线散射和衍射方法。我们对酶特别感兴趣 生物医学的重要性一直难以通过传统方法进行研究，例如药物靶标 是变构调节的酶，其复杂的机制可合成天然产物与药物 美容潜力。