STRUCTURES OF DIHYDROOROTASE AND OTHER ENZYME-LIGAND COMPLEXES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 二氢核糖核酸酶、5-(羧氨基)咪唑核糖核苷酸变位酶、N5-羧氨基咪唑核糖核苷酸合成酶和血影蛋白的几种配体复合体的结构研究正在进行中。我们正在对这份清单中的前三种酶进行高通量筛选和电子筛选，以开发新的化合物抑制剂支架，从而开发新的广谱抗生素类别。最初，我们的目标是炭疽杆菌、镰刀菌、结核分枝杆菌和金黄色葡萄球菌的二氢脱氢酶。对血影蛋白复合体的研究与了解细胞凋亡的机制密切相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Structural studies on several ligand complexes of dihydroorotase, 5-(carboxyamino)- imidazole ribonucleotide mutase, and N5-carboxyaminoimidazole ribonucleotide synthetase, and spectrin are ongoing. We are carrying out high-throughput screening and in-silico screening on first three enzymes in this list, to develop new chemical compound inhibitor scaffolds and thus, new classes of broad spectrum antibiotics. Initially, we are targeting dihydroorotase from B. anthracis, P. falciparem, M. tuberculosis, and S. aureus. The study of spectrin complexes is linked to understanding the mechanism of apotosis.