Protein Dynamics and Chemical Reactivity in Microbial Hemoglobins

化学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教授对来自结核分枝杆菌、空肠弯曲杆菌和大肠杆菌三种微生物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，但目标血红蛋白通过利用分子氧参与抵抗一氧化氮（先天宿主免疫系统的关键杀菌剂）的防御机制。该项目的目的是确定这些有趣的氧利用珠蛋白的功能特性，并确定这些特性由每个珠蛋白中容纳假血红素组的蛋白质基质决定的机制。为了实现这一目标，将开发一套互补的光谱和快速动力学技术，结合生化和计算方法，并以迭代的方式使用。本课题的成功完成将更好地明确细菌球蛋白的生理作用和功能机制，这是该领域缺乏的，从而推进血红素蛋白结构-功能关系的基础知识。由此获得的知识将为设计携带分子氧的高效血液代用品或为制药应用执行氧化学的合格人工酶提供有价值的指导。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、教育和指导年轻科学家，特别是妇女和代表性不足的少数民族方面的持续努力。

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.