Hemoglobin I From Lucina Pectinata: A Model for Hydrogen Sulfide Reactivity Within Hemeproteins

热带蛤蜊Lucina pectinata生活在富含硫化物的环境中，其特征是存在共生的硫化物氧化细菌，需要同时提供H2S和O2。负责将H2S输送到细菌的生物分子是一种名为血红蛋白I（HbI）的血红素蛋白。HbI是生物体中为数不多的已知H2S载体之一，其在生理学上与亚铁血红素铁中心中的该分子结合，以维持与细菌的共生关系以及保护蛤免受H2S毒性。一个透彻的理解的协会，稳定性和解离机制的生理相关的H2S配体与HbI和其他血红素蛋白尚未建立。在这个项目中，HbI-H2S复合物的结构和反应性之间的关系将进行研究，以确定血红素口袋中的氨基酸的化学性质如何影响血红素蛋白中的H2S结合和氢键相互作用。将使用分子生物学和生物物理技术相结合的方法。此外，将检查HbI-H2S NMR化学位移和HbI-H2S部分的EXAFS距离的相关性。 该项目的智力价值是确定H2S和HbI的结构、动力学和反应性，并了解血红蛋白向共生细菌释放H2S的机制。了解生物物理基础H2S运输的HbI可以帮助在未来发展的生物传感器检测H2S在生态和生物环境中; H2S是一种已知的有毒化合物。更广泛的影响：这个跨学科的项目将被用作教学工具，指导研究生和本科生，并增加他们的知识和沟通能力，向社会表达研究成果。 因此，对社会的更广泛影响是增加能够充分实现其学术或工业生涯的训练有素的学生人数所固有的。该项目还将通过GK-12计划加强对大学预科学生和教师的宣传。

The tropical clam Lucina pectinata lives in sulfide-rich environments and is characterized by the presence of symbiotic sulfide-oxidizing bacteria that need to be supplied with both H2S and O2. The biological molecule responsible for delivering H2S to the bacteria is a heme protein called hemoglobin I (HbI). HbI is one of the few known H2S carriers in organisms that have been implicated in physiologically binding this molecule in the ferric heme iron center so as to maintain the symbiotic relationship with the bacteria as well as to protect the clam from H2S toxicity. A thorough understanding of the association, stabilization, and dissociation mechanism of the physiological relevant H2S ligand with HbI and other heme proteins has not been established yet. In this project, the relationship between structure and reactivity of the HbI-H2S complex will be investigated to define how the chemical nature of the amino acids in the heme pocket affects H2S binding and hydrogen bonding interactions in heme proteins. A combination of molecular biology and biophysical techniques will be used. In addition, correlations of HbI-H2S NMR chemical shifts and EXAFS distances of the HbI-H2S moiety will be examined. The intellectual merits of the project are to determine the structure, dynamics, and reactivity of H2S and HbI and to understand the mechanism of H2S release by the hemoglobin to the symbiotic bacteria. Understanding the biophysical basis H2S transport by HbI could help in the future developments of a biosensor to detect H2S in ecological and biological environments; H2S is a known toxic compound.Broader Impacts: This interdisciplinary project will be used as teaching tools to mentor graduate and undergraduate students and to increase their knowledge and communication abilities to express research results to society. Consequently, the broader impacts to society are inherent to increasing the number of well-trained students capable of fully achieving their academic or industrial career. The project will also enhance outreach to pre-college students and teachers through the GK-12 program.