STRUCTURAL DETERMINATIONS OF GLUTAMINE-DEPENDENT NAD SYNTHETASES AND OF ENZYMES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 1)谷氨酰胺？依赖性NAD+合成酶催化NAD+生物合成中从头和再循环途径的最后一步。这种酶是复制和非复制M的生存所必需的。结核病，因此它是一个有吸引力的药物靶标。在人类中，NAD合成酶非依赖性途径参与NAD生物合成。我们正在研究H的结构和动力学特征。sapiens和M.结核酶2)吡咯并苯并二氮杂卓类化合物是一类具有较强抗肿瘤活性的天然产物。 我们正在研究这些化合物的生物合成，我们已经确定了两种催化不寻常化学反应的酶，并且在PBD数据库中没有同源性。因此，第二个项目包括这些前所未有的参与吡咯并苯并二氮杂生物合成的酶的结构测定。

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. 1) Glutamine?dependent NAD+ synthetase catalyzes the last step of the de novo and recycling pathways in NAD+ biosynthesis. This enzyme is essential for survival of replicating and non-replicating M. tuberculosis and as such it is an attractive drug target. In humans NAD synthetase independent pathways participate in NAD biosynthesis. We are working on the structural and kinetic characterizations of the H. sapiens and M. tuberculosis enzymes. 2) Pyrrolobenzodiazepine are natural products with strong antitumor properties. We are studying the biosynthesis of these compounds and we have identified two enzymes that catalyze unusual chemical reactions and that have no homologous in the PBD database. Therefore, the second project includes the structural determination of these unprecedented enzymes involved in pyrrolobenzodiazepine biosynthesis.