Dynamics, Catalysis, and Residue Networks within a Phosphohexomutase

磷酸己糖变位酶内的动力学、催化和残基网络

• 批准号: 0918389
• 负责人: Lesa Beamer
• 金额: $ 104.41万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0918389&HistoricalAwards=false
• 关键词: Dynamics; Catalysis; Residue; Networks; within

Intellectual meritEnzymes are responsible for the many chemical reactions that allow life to occur. To really understand how enzymes work, both their three-dimensional shapes and the molecular motions that they undergo must be studied. New information suggests that protein structure and movements are connected in a very complex fashion, via "pathways" of amino acid residues. This important issue will be studied in an enzyme from the bacterium P. aeruginosa. This enzyme (called phosphomannomutase/phosphoglucomutase or PMM/PGM) helps the bacteria produce polysaccharides and other sugar-containing products. Because its three-dimensional structure has already been carefully studied, it is an excellent system for investigating the complicated question of how structure and movements are related. In particular, the project involves use of biophysical techniques, including nuclear magnetic resonance, to create a detailed picture of the molecular movements and fluctuations that permit the enzyme to perform its catalytic reaction. These studies will help find the hidden pathways of amino acids involved in these processes. Understanding these pathways may eventually help researchers design new types of proteins, such as faster and more efficient enzymes, that can be used in industry or medicine. Broader ImpactThese studies are at the interface of structural biology, enzymology, and computational biology. Both undergraduate and graduate students will participate in this work and gain valuable experience in this emerging, interdisciplinary area. Special emphasis for training opportunities will be given to women and minority students. In addition, parts of the experimental studies will be incorporated into the graduate level curriculum in the Biochemistry department, allowing many students to gain insights into these important issues.

酶负责许多使生命得以发生的化学反应。 要真正了解酶是如何工作的，必须研究它们的三维形状和它们所经历的分子运动。 新的信息表明，蛋白质的结构和运动是通过氨基酸残基的“途径”以非常复杂的方式连接起来的。 这一重要问题将在铜绿假单胞菌的酶中进行研究。 这种酶（称为磷酸甘露变位酶/磷酸葡萄糖变位酶或PMM/PGM）帮助细菌产生多糖和其他含糖产物。 因为它的三维结构已经被仔细研究过了，所以它是研究结构和运动如何联系的复杂问题的一个极好的系统。 特别是，该项目涉及使用生物物理技术，包括核磁共振，以创建允许酶进行催化反应的分子运动和波动的详细图像。 这些研究将有助于发现参与这些过程的氨基酸的隐藏途径。 了解这些途径最终可能有助于研究人员设计新型蛋白质，例如更快，更有效的酶，可用于工业或医学。 更广泛的影响这些研究是在结构生物学，酶学和计算生物学的接口。 本科生和研究生都将参与这项工作，并在这一新兴的跨学科领域获得宝贵的经验。 将特别重视妇女和少数民族学生的培训机会。 此外，部分实验研究将纳入生物化学系的研究生课程，使许多学生能够深入了解这些重要问题。