PHAGE INFECTION STRUCT OF G3P IN COMPLEX W/ CORECEPTOR, C TERMINAL DOMAIN

具有辅助受体、C 末端结构域的复合体中 G3P 的噬菌体感染结构

• 批准号: 6205776
• 负责人: ALEX WLODAWER
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205776
• 关键词: biological products; biomedical resource; enzymes; growth /development; spectrometry

Dr. Steven Almo, an x-ray crystallographer with significant synchrotron experience, has spearheaded a collaborative effort in conjunction with Dr. Zhong-Yin Zhang, an enzymologist, and Dr. David Lawrence, a synthetic chemist. The goal of this project is the structure-based design of potential therapeutic agents which bind to protein tyrosine phosphatases (PTPases), and the elucidation of the structures of novel PTPases. Since data collected on rotating anode sources at AECOM were of insufficient resolution, single-crystal diffraction data collected at beamline X9B has been absolutely essential for current progress. H Using synchrotron methods, Dr. Almo's group has solved the Hstructure of human protein tyrosine phosphatase 1B (PTP1B) in complex Hwith several different substrates, using 1.9A data collected at X9B. HThe complex of PTP1B and a synthetic high-affinity non-peptide Hsubstrate synthesized by the Lawrence group has demonstrated the Hexistence of a novel aryl phosphate binding site, which provides a new Hparadigm for the design of tight-binding inhibitors. This is the Hhighest resolution reported for this enzyme and this work has recently Hled to a publication in PNAS. Based on these findings, the Lawrence Hlab has synthesized a series second generation of PTP1B ligands that Hencompass both aryl phosphate functionalities and data has been Hcollected at X-9B on several different complexes.

史蒂文·阿尔莫博士是一位X射线晶体学家， 同步加速器的经验，带头合作， 与酶学家张中银博士和大卫博士一起 劳伦斯，合成化学家。 该项目的目标是 基于结构设计结合 蛋白酪氨酸磷酸酶（PTPases），并阐明 新型PTPases的结构。 由于在旋转阳极上收集的数据 AECOM的源分辨率不足，单晶 在光束线X9 B处收集的衍射数据已经完全 对当前的进展至关重要。 H使用同步加速器的方法，博士。 Almo的小组已经解决了人类蛋白酪氨酸的H结构 磷酸酶1B（PTP 1B）与几种不同底物的复合物H， 使用在X9 B收集的1.9A数据。 PTP 1B与a的复合物 合成的高亲和力非肽H底物， Lawrence群证明了一个新的芳基的存在性 磷酸结合位点，为设计提供了一种新的H范式 紧密结合的抑制剂。 这是报告的H最高分辨率 这项工作最近发表在 PNAS. 基于这些发现，Lawrence Hlab合成了一种 系列第二代PTP 1B配体，Hencompass均为芳基 磷酸盐功能和数据已在X-9 B上收集， 几种不同的复合物。