STRUCTURAL STUDIES OF MEMBERS OF THE DJ-1 SUPERFAMILY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 DJ-1超家族是一个庞大而多样的蛋白质组，在大多数生命王国中都有代表。 人类DJ-1是一种蛋白质，可以保护细胞免受氧化应激，并与帕金森？的疾病和某些类型的癌症。 DJ-1超家族的许多其他成员已被部分表征，并在各种生物对环境胁迫的反应中发挥重要作用。 我们感兴趣的是确定1）DJ-1超家族中相关但功能不同的蛋白质如何使用相似的结构特征来实现不同的生物学作用，以及2）翻译后修饰如何调节这些蛋白质的功能。 我们正在研究DJ-1从几个物种（人，果蝇，大肠杆菌），一个相关的蛋白质从荧光假单胞菌的功能作为异腈水合酶，和几个一般的压力反应蛋白的DJ-1超家族。我们和我们的合作者已经表明，果蝇和E。大肠杆菌DJ-1同源物与人类蛋白质在功能上是可互换的，并将使用结构信息来确定这些疾病相关蛋白质是如何调节的。在一个相关的项目中，我们已经表明，异腈水合酶催化各种异腈转化为酰胺，并采用DJ-1超家族中保守的氨基酸来完成这种独特的化学反应。我们还在研究一个不寻常的植物特异性DJ-1蛋白进化枝的结构，该进化枝由两个融合的DJ-1样结构域组成。我们已经收集了这些蛋白质中的每一个使用旋转阳极源在UNL晶体的数据集。这些结构中的每一个都已经通过分子置换成功地解决了，我们将在APS收集的改进数据将有助于模型的改进、分析和出版。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The DJ-1 superfamily is a large and diverse set of proteins that has representatives in most kingdoms of life. Human DJ-1 is protein that protects cells against oxidative stress, and in implicated in both Parkinson?s disease and certain types of cancer. Many other members of the DJ-1 superfamily have been partially characterized and play important roles in the response of various organisms to environmental stress. We are interested in determining 1) how related but functionally distinct proteins in the DJ-1 superfamily use the similar structural features to fulfill different biological roles and 2) how posttranslational modifications regulate the functions of these proteins. We are studying DJ-1 from several species (Human, Drosophila melanogaster, Escherichia coli), a related protein from Pseudomomas fluorescens that functions as an isonitrile hydratase, and several general stress response proteins in the DJ-1 superfamily. We and our collaborators have shown that the Drosophila melanogaster and E. coli DJ-1 homologues are functionally interchangeable with the human protein, and will use structural information to determine how these disease-related proteins are regulated. In a related project, we have shown that isonitrile hydratase catalyzes the conversion of various isonitriles to amides and employs amino acids that are well-conserved in the DJ-1 superfamily to accomplish this unique chemistry. We are also investigating the structures of an unusual clade of plant-specific DJ-1 proteins that are composed of two fused DJ-1-like domains. We have collected datasets on crystals of each of these proteins using the rotating anode source at UNL. Each of these structures has been successfully solved by molecular replacement and the improved data that we will collect at the APS will aid in model refinement, analysis, and publication.