CRYSTAL STRUCTURE OF NON-RIBOSOMAL PEPTIDE SYNTHETASES AND RELATED PROTEINS

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。非核糖体多肽合成酶是一种模块化的多结构域酶，可合成经常显示抗生素活性的多肽。这些酶有多个催化结构域连接到一条装配线上，以催化多肽产品的顺序延伸。我们感兴趣的是从结构上研究这些蛋白质，以提供这些不同的催化结构域如何相互作用的线索。我们的研究集中在NRPS腺化结构域，它与氨基酸结合，并将它们共价连接到NRPS载体蛋白结构域的泛氨酸辅助因子上。我们希望收集--更高分辨率的数据，以获得更好的EntB蛋白模型--用于HBAL结构确定的MAD数据--CBAL的几种突变酶的高分辨率数据，以验证结构域交替假说。

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 Non-Ribosomal Peptide Synthetases are modular, multidomain enzymes that synthesize peptides that frequently show antibiotic activity. These enzymes have multiple catalytic domains joined in an assembly line to catalyze the sequential elongation of the peptide product. We are interested in studying these proteins structurally to provide clues to how these distinct catalytic domains interact. Our studies are focused on the NRPS adenylation domains that bind to amino acids and covalently attach them to a pantetheine cofactor of an NRPS carrier protein domain. We wish to collect --higher resolution data to obtain a better model for the EntB protein --MAD data for the HBAL structure determination --high resolution data on several mutant enzymes of the CBAL to test the Domain Alternation hypothesis.