CAREER: Glycoside Hydrolase Processivity and Substrate Recognition Mechanisms

摘要：佩恩（1552355）拟议的研究将提供动力学和热力学的基本理解，一类酶，称为糖苷水解酶（GH），催化生物质分解成糖，可以进一步加工成燃料和化学品。 由此获得的知识将指导这些酶的生物工程，以提高其效率并降低可再生生物基方法的成本，以实现可持续能源的未来。 生长激素分解结晶生物质材料，如纤维素或甲壳素的持续合成能力-重复催化-或咀嚼掉-的债券，保持生物质材料在一起。 与GH和生物质材料的详细结构和组成相关的许多因素影响持续合成能力。 虽然加工机制一直是许多结构和生物化学研究的焦点，酶的结构和加工功能之间的明确联系仍然缺乏。 为此，拟议的研究重点是通过实验生化表征支持的分子建模和热力学计算，从分子水平上了解GH持续合成能力的机制-后者是与一个国际研究团队一起进行的。 虽然这项工作将主要针对模型GH系统利用几丁质酶，目标将是开发一个广义的GH合成能力的理论，将在更常见的（和更复杂的）纤维素材料，最终将形成一个可再生的生物质燃料工业的基础进行评估。 该提案还涉及教育和外联的相关内容-特别是研究生的国际研究经验，向服务不足的研究界传播高性能计算工具，以及向年轻女孩开展外联活动，旨在激发她们对科学和工程，特别是生物化学领域的机会的兴趣。

Abstract: Payne (1552355)The proposed research will provide fundamental understanding of the kinetics and thermodynamics by which a class of enzymes, known as glycoside hydrolases (GHs), catalyze the breakdown of biomass into sugars that can be processed further to fuels and chemicals. The knowledge thus obtained will guide the bioengineering of these enzymes to improve their efficiency and reduce the cost of renewable bio-based approaches to a sustainable energy future. GHs break down crystalline biomass material such as cellulose or chitin by processivity - the repeated catalysis - or chewing away - of the bonds that hold the biomass material together. A number of factors related to the detailed structure and composition of both the GH and the biomass material affect the processivity. Although the processive mechanism has been the focus of numerous structural and biochemical studies, a clear connection between enzyme structure and processive function is still lacking. To this end, the proposed research focuses on developing a molecular-level understanding of the mechanisms governing GH processivity through molecular modeling and thermodynamic calculations backed by experimental biochemical characterization - the latter carried out with an international team of researchers. Although the work will primarily be directed at a model GH system utilizing chitinases, the goal will be to develop a generalized theory of GH processivity that will be assessed in the more common (and more complicated) cellulosic materials that will eventually form the basis of a renewable biomass fuel industry. The proposal also involves related elements of education and outreach - notably international research experiences for graduate students, dissemination of high performance computing tools to underserved research communities, and outreach to young girls aimed at exciting them about opportunities in science and engineering, especially in the biochemical area.