HIGH RESOLUTION SAR STUDIES ON CAVITY MUTANTS OF CYTOCHROME C PEROXIDASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本文研究了血红素酶细胞色素c过氧化物酶（CCP）的空腔突变体W51 A的结构-亲和关系（SAR）。将单一和混合配体溶液浸泡到疏水性CCP腔中，结合配体的分配将取决于电子密度的质量，而电子密度的质量又取决于一种特定配体和一种结合模式的位点特异性。最初，内部数据已经收集到配体渗入这种突变体，但电子密度缺乏必要的细节，以区分某些原子的身份和它们的手性。使用同步辐射的高分辨率X射线晶体学将提供正确识别浸入CCP中的不同对映体产物所需的详细信息。这些类型的研究将进一步有助于更好地理解蛋白质-配体相互作用，这反过来又将推进基于结构的药物设计和蛋白质工程领域。

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. Structure-affinity relationships (SAR) will be studied in a cavity mutant, W51A, of the heme enzyme, cytochrome c peroxidase (CCP). Single and mixed ligand solutions will be soaked into the hydrophobic CCP cavity and assignment of the bound ligand(s) will depend on the quality of the electron density which in turn is dependent on the specificity of the site for one particular ligand and one binding mode. Initial, in-house data has been collected on ligand soaks into this mutant, but the electron density lacks the detail necessary to distinguish the identity of certain atoms and their chirality. High resolution x-ray crystallography using synchrotron radiation will provide the detailed information required to correctly identify the different enantiomeric products soaked into CCP. These types of studies will further contribute to a better understanding of protein-ligand interactions which in turn will advance the fields of structure-based drug design and protein engineering.