LEINAMYCIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大自然为我们提供了大量结构多样的天然产品，我们用这些产品来抗击从普通感冒到癌症的各种疾病。细菌和其他有机体如何制造这些化合物的问题需要调查。我们正在研究几种在其生物合成途径中具有非常有趣的活性的蛋白质。LnmQ是雷诺霉素生物合成途径中的一个腺化结构域，它特异性地激活D-丙氨酸。这是唯一已知的针对非天然立体异构体的腺化结构域。这项提议将使用X射线结晶学技术来确切地确定这种酶是如何工作的，以及它如何识别像D-ALA这样的小疏水侧链。已经为这种蛋白质生长了天然晶体和Se-Met晶体。它们已经在我们的家乡进行了筛选，我们已经能够获得关于空间群和单胞尺寸的信息。LnmQ的空间群为C2，晶胞参数为a=97.714，b=102.412，c=79.008，其中？=90，？=116.973，？=90。

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. Nature has given us a tremendous amount of structurally diverse natural products which we use to combat diseases ranging from the common cold to cancer. The question of how bacteria and other organisms make these compounds needs to be investigated. We are investigating several proteins that have very interesting activity in their biosynthetic pathways. LnmQ is an adenylation domain in the leinamycin biosynthetic pathway which specifically activates D-Ala. This is the only known adenylation domain to be specific for the unnatural stereoisomer. This proposal will use the technique of X-ray crystallography to determine exactly how this enzyme works mechanistically and how it can recognize a small hydrophobic side chain such as that of D-Ala. Native and Se-Met crystals have been grown for this protein. They have been screened at our home source and we have been able to get information regarding space group and unit cell dimensions. LnmQ has a space group of C2 and a unit cell of a=97.714, b=102.412, c=79.008 with ¿}¿¿=90, ¿}¿¿=116.973, ¿}¿¿=90.