Structure/Function Relations of the Anti HIV Protein, Map30

抗 HIV 蛋白的结构/功能关系，Map30

• 批准号: 6104685
• 负责人: DENNIS A TORCHIA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6104685
• 关键词: antiAIDS agent; antineoplastics; antiviral agents; human immunodeficiency virus; molecular dynamics; nuclear magnetic resonance spectroscopy; plant proteins; protein structure function; solutions

Map30 is an anti-HIV and anti-tumor multi-functional protein extracted from the matured fruits and seeds of Momordica charantia (bitter melon). The sequence of the protein identifies MAP 30 as a member of the family of ribosomal inactivating proteins of which Ricin A is the most well known. However, Map 30 has been reported to have activities not shared by other RIPs. In order to understand its functionality at the molecular level, we have undertaken to determine its three dimensional solution structure. Although the size of the protein, 30kDa., makes this a formidable task, we have recently solved the solution structure of the protein using NMR spectroscopy, based upon ca. 4000 angle and distance constraints and 300 residual dipolar couplings. Our structure reveals that the fold of MAP 30 is quite similar to the structures of ricin A and to homologous type I RIPs whose crystal structures are available. This observation raises the question as to how MAP30 can have several distinct activities not shared by ricin A and other RIPs. A recent report (Barbieri et al. Nuc Acid Res (1997) 25, 518) suggest RIPs are generally able cleave adenine from DNA substrates. These results together with the structural information suggest that MAP30 and other type I RIPs may have similar biological activities. We are reexamining the question of the biological activity of our recombinant MAP30 samples in the light of this new information about the protein's structure.

MAP30是一种反HIV和抗肿瘤 从成熟的水果和种子中提取的多功能蛋白 Momordica Charantia（苦瓜）。蛋白质的序列 将地图30识别为核糖体系列的成员 ricin A的灭活蛋白是最著名的。 但是，据报道，地图30没有共享活动 由其他撕裂。为了了解其功能 分子水平，我们已承诺确定其三个 维溶液结构。虽然蛋白质的大小，但 30kda。使这是一项艰巨的任务，我们最近解决了 基于NMR光谱法，蛋白质的溶液结构 在大约4000角和距离约束和300个残留 偶极耦合。我们的结构表明，地图30的折叠是 与Ricin A的结构和同源I类型非常相似 可用的晶体结构的撕裂。这种观察提出了 关于MAP30如何进行几个不同活动的问题 Ricin A和其他撕裂没有共享。最近的报告（Barbieri et al。 Niw Acid Res（1997）25，518）表明撕裂通常能够 DNA底物裂解腺嘌呤。这些结果与 结构信息表明MAP30和其他类型I 撕裂可能具有类似的生物学活动。我们正在重新审视 我们重组MAP30的生物活性问题 根据有关该蛋白质的新信息的样品 结构。