LEINAMYCIN

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 大自然给了我们大量结构多样的天然产品，我们用它们来对抗从普通感冒到癌症的各种疾病。细菌和其他生物如何制造这些化合物的问题需要研究。我们正在研究几种在其生物合成途径中具有非常有趣活性的蛋白质。LnmQ是来那霉素生物合成途径中的腺苷酸化结构域，其特异性激活D-Ala。这是唯一已知的特异性针对非天然立体异构体的腺苷酸化结构域。该提案将使用X射线晶体学技术来确定这种酶的确切工作机制以及它如何识别小的疏水侧链，如D-Ala。天然和Se-Met晶体已经生长这种蛋白质。他们已经在我们的家庭来源筛选，我们已经能够得到有关空间群和晶胞尺寸的信息。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.