Protein Dynamics and Chemical Reactivity in Microbial Hemoglobins

微生物血红蛋白的蛋白质动力学和化学反应性

• 批准号: 0956358
• 负责人: Syun-Ru Yeh
• 金额: $ 53万
• 依托单位: Yeshiva University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956358&HistoricalAwards=false
• 关键词: Protein; Dynamics; Chemical; Reactivity; Microbial

This award in the Chemistry of Life Processes program of the Chemistry Division is co-funded by the Biomolecular Systems Cluster in the Division of Molecular and Cellular Biosciences. The award supports work by Professor Syun-Ru Yeh at the Albert Einstein College of Medicine to carry out comparative studies of five novel hemoglobins from three microorganisms, Mycobacterium tuberculosis, Campylobacter jejuni and Escherichia coli. Although hemoglobins are commonly perceived as oxygen carriers, the target globins have been implicated in defense mechanisms against nitric oxide, a key bactericidal agent of the innate host immune system, by utilizing molecular oxygen. The objective of this project is to determine the functional properties of these intriguing oxygen-utilizing globins and to define the mechanism by which these properties are dictated by the protein matrix housing the prosthetic heme group in each globin. To achieve the goal, a complementary set of spectroscopic and rapid-kinetic techniques, combined with biochemical and computational methodologies will be developed and employed in an iterative fashion. The successful completion of this project will better define the physiological roles and functional mechanisms of the bacterial globins that is lacking in the field, thereby advancing fundamental knowledge in the structure-function relationships of heme-proteins. The knowledge thus derived will offer valuable guidelines for the design of efficient blood substitutes carrying molecular oxygen or competent artificial enzymes performing oxygen chemistry for pharmaceutical applications. The multifaceted approach is expected to provide unique training opportunities for graduate, undergraduate and high school students, thereby enhancing the PI's continuing efforts in recruiting, educating and mentoring young scientists, especially women and under-represented minorities.

化学部生命过程化学项目的这个奖项是由分子和细胞生物科学部的生物分子系统集群共同资助的。该奖项支持阿尔伯特·爱因斯坦医学院的Syun-Ru Yeh教授对来自三种微生物（结核分枝杆菌、空肠弯曲杆菌和大肠杆菌）的五种新型血红蛋白进行比较研究。虽然血红蛋白通常被认为是氧载体，但靶球蛋白通过利用分子氧参与了针对一氧化氮的防御机制，一氧化氮是先天宿主免疫系统的关键杀菌剂。 本项目的目的是确定这些有趣的氧利用球蛋白的功能特性，并确定这些特性是由蛋白质基质住房的假体血红素组在每个球蛋白的机制。为了实现这一目标，将开发一套补充的光谱和快速动力学技术，结合生物化学和计算方法，并以迭代的方式使用。该项目的成功完成将更好地定义该领域缺乏的细菌球蛋白的生理作用和功能机制，从而推进血红素蛋白的结构-功能关系的基础知识。由此得出的知识将提供有价值的指导方针，设计有效的血液替代品携带分子氧或主管人工酶进行氧化学制药应用。这种多方面的方法预计将为研究生、本科生和高中生提供独特的培训机会，从而加强PI在招募、教育和指导青年科学家，特别是妇女和代表性不足的少数民族方面的持续努力。