STRUCTURE OF PROLIDASE, A PROLINE-SPECIFIC DIPEPTIDASE WITH A DINUCLEAR METAL CE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。Prolidase是一种普遍存在的酶，参与了Pro多肽的降解。在哺乳动物中，脯氨酸酶是胶原合成所需的脯氨酸循环所必需的。我们正在寻求解决哺乳动物和细菌的脯氨酸酶的结构，以期确定其特异性的基础。我们已经从超嗜热性的P.Furiosus中分离出了第一个适合我们的晶体的脯氨酸酶。据报道，该酶的活性部位含有一个双核钴中心。令人惊讶的是，SSRL在2000年记录的数据明确表明，这些晶体的活性部位含有锌。我们现在寻求记录在抑制剂或底物存在下生长的晶体的数据，以帮助定义酶机制。

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. Prolidases are ubiquitous enzymes involved in the degradation of proline peptides. In mammals, prolidases are essential for the recycling of proline required for collagen synthesis. We are seeking to solve the structures of both mammalian and bacterial prolidases, with a view to defining the basis of their specificity. The first prolidase for which we have suitable crystals has been isolated from the hyper-thermophile, P. furiosus. The active site of this enzyme is reported to contain a dinuclear cobalt center. Surprisingly data recorded at SSRL in 2000 showed unequivocally that the crystals contained zinc at the active site. We now seek to record data from crystals grown in the presence of inhibitors or substrate to help define the enzyme mechanism.