STRUCTURE OF HEXAMERIC BUNDLES OF BETA-AMINO ACID PEPTIDE U1F

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。U1F：b3Glu-b3Leu-b3Orn-b3Phe-b3Leu-b3Asp-b3Phe-b3Leu-b3Orn-b3Orn-b3Leu-b3Asp其中b3Xxx是指对应于α-氨基酸Xxx的同源结合产物的3-取代的β-氨基酸。Orn =鸟氨酸。 我们已经合成了U1F，一种β-氨基酸十二肽，其在水中协同折叠形成稳定的同六聚体。用氘交换核磁共振实验和圆二色性测定对其折叠进行了表征。其在溶液中的低聚状态被指定为一个六聚体的分析超离心。我们已经获得了晶体，其折射率约为3埃在我们的家庭来源（耶鲁大学结构生物学中心）。空间群为P42212，晶胞尺寸为43 × 43 × 75埃。这与含有六聚体U1F束的晶胞一致。在CHESS，我们希望获得更高分辨率的衍射数据，目前这受到晶体尺寸和源强度的限制。我们正在筛选衍生物，以便逐步采用我们的本土来源，也可能带来经确认的衍生物，用于高分辨率数据收集。 六聚体U1F代表了由非天然β-氨基酸组成的分子中三元结构的第一个例子。U1F也是重要的，因为它是最小的（12聚体）四级结构之一，天然或非天然的，显示合作折叠过渡。U1F被设计为基于从β肽二级结构和亮氨酸拉链三元结构的研究中收集的原理折叠和寡聚化。合理设计的折叠聚合物代表了我们对自然（即蛋白质）和非自然系统中控制折叠的力的理解的重要证明。因此，我们期望U1F的高分辨率结构将引起化学和生物界的普遍兴趣。 彼得森博士获得了博士学位。在加州理工学院的丹尼斯·道格尔的实验室里，通过合成氨基酸来研究蛋白质的结构和功能。丹尼尔斯博士获得了博士学位。在斯克里普斯的约翰·泰纳的实验室里，通过X射线晶体学研究DNA修复酶。

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. U1F: b3Glu-b3Leu-b3Orn-b3Phe-b3Leu-b3Asp-b3Phe-b3Leu-b3Orn-b3Orn-b3Leu-b3Asp where b3Xxx refers to the 3-substituted beta-amino acid corresponding to the homoligation product of alpha-amino acid Xxx. Orn = ornithine. We have synthesized U1F, a beta-amino acid dodecapeptide, which folds cooperatively to form a stable homohexamer in water. Its folding has been characterized by deuterium exchange NMR experiments and circular dichroism measurments. Its oligomeric state in solution was assigned to be a hexamer by analytical ultracentrifugation. We have obtained crystals which diffract to approximately 3 angstroms on our home source (Yale Center for Structural Biology). We have assigned the space group to P42212 and the unit cell dimensions to 43 X 43 X 75 angstroms. This is consistent with a unit cell containing a hexameric U1F bundle. At CHESS, we hope to obtain significantly higher resolution diffraction data, which is currently limited by crystal size and source intensity. We are screening derivatives for phasing on our home source and may also bring confirmed derivatives for high resolution data collection. The hexameric U1F represents the first example of ternary structure in a molecule composed of unnatural beta-amino acids. U1F is also significant because it is one of the smallest (12mer) quaternary structures, natural or unnatural, to display a cooperative folding transition. U1F has been designed to fold and oligomerize based on principles gleaned from studies of beta-peptide secondary structure and leucine zipper ternary structure. Rationally designed folded polymers represent an important demonstration of our understanding of the forces which govern folding in both natural (i.e. protein) and unnatural systems. Therefore, we expect that a high resolution structure of U1F will be of great general interest to both the chemistry and biology communities. Dr. Petersson received his Ph.D. studying protein structure and function through synthetic amino acid incorporation in the labs of Dennis Dougherty at Caltech. Dr. Daniels received his Ph.D. studying DNA repair enzymes through x-ray crystallography in the labs of John Tainer at Scripps.