International Collaboration in Chemistry:ELECTRONIC STRUCTURE OF BIOLOGICAL METALLO-CLUSTER AND ITS MAGNETIC INTERPLAY WITH THE PROTEIN SURROUNDING IN THERMOPHILE METALLOENZYMES

化学部生命过程化学(CLP)项目的国际化学合作(ICC)奖支持伊利诺伊大学厄巴纳-香槟分校的Sergei Dikanov教授与日本日本医科大学的Toshio Iwa aki博士和日本同步辐射研究所(JASRI)/Spring-8的Takashi Kumasaka博士合作，研究蛋白质环境对还原的[2Fe-2S]团簇电子结构的影响，其中铁(II)中心的配体可以是(Cys)2，(His)1(Cys)，1或(His)2。本项目将探索团簇和邻近关键氨基酸残基上未配对自旋密度分布的完整三维景观，以确定在高温易处理的铁硫蛋白中对还原的[2Fe-2S]团簇的电子结构具有主要影响的残基。为了实现这一目标，一套互补的多频率脉冲EPR方法将应用于野生型蛋白质，使用冷冻溶液和单晶，以及具有均匀和特定位置的稳定同位素(2H，15N，13C，57Fe)替代的蛋白质。光谱方法将与超高分辨率X射线结晶学和理论计算相结合。该项目将为青年科学家提供极好的培训机会，他们将通过双向访问获得宝贵的多学科国际研究经验。该项目由NSF和日本科学促进会(JSPS)共同支持，所有主要的电子转移链都包含铁硫簇合物，簇合物的环境是氧化还原和/或催化活性的主要决定因素。它们在能量转换的催化作用中的作用在光合作用、呼吸作用和许多辅助代谢过程中都是至关重要的。我们对这些决定因素的了解对于更深入地了解这些过程是如何工作的至关重要，对于了解如何优化这些过程至关重要，例如在生物燃料的生产中。

This International Collaboration in Chemistry (ICC) award in the Chemistry of Life Processes (CLP) program in the Division of Chemistry supports work by Professor Sergei Dikanov from the University of Illinois at Urbana-Champaign, in collaboration with Dr. Toshio Iwasaki of Nippon Medical School, Japan, and Dr. Takashi Kumasaka of Japan Synchrotron Radiation Research Institute (JASRI)/SPring-8, to study the influence of the protein environment on the electronic structure of the reduced [2Fe-2S] clusters, in which the ligands to the iron(II) site can be (Cys)2, (His)1(Cys)1, or (His)2. This project will explore the complete three-dimensional landscape of the unpaired spin density distribution over the cluster and neighboring key amino acid residues in order to identify the residues having the major influence on the electronic structure of the reduced [2Fe-2S] cluster in hyperthermophilic tractable iron-sulfur proteins. To achieve the goal, a complementary set of multifrequency pulsed EPR approaches will be applied to wild-type proteins, using frozen solutions and single-crystals, and to proteins with uniform and site-specific stable isotopic (2H, 15N, 13C, 57Fe) substitution. The spectroscopic approaches will be combined with ultrahigh-resolution X-ray crystallography, and theoretical calculations. This project will provide excellent training opportunities to young scientists who will gain invaluable multidisciplinary international research experience via bidirectional visits. This project is jointly supported by the NSF and the Japan Society for the Promotion of Science (JSPS).All major electron transfer chains incorporate iron-sulfur clusters, and the environment of the cluster is the main determinant of the redox and/or catalytic activity. Their roles in catalysis of energy conversion are of central importance in photosynthesis, respiration, and many ancillary metabolic processes. Our understanding of these determinants is essential to a deeper knowledge how these processes work, and of critical importance in knowing how to optimize such processes, for example in generation of biofuels.