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

史蒂文·阿尔莫博士，一位X射线结晶学家 同步加速器体验，引领了一项合作努力 与酶学家张忠银博士和大卫博士合作 劳伦斯，一位合成化学家。这个项目的目标是 基于结构的潜在治疗剂的设计 蛋白酪氨酸磷酸酶(PTPase)的研究进展 新型PTPase的结构。由于在旋转阳极上收集的数据 AECOM的震源分辨率不够高，为单晶 在光束线X9B收集的衍射数据绝对是 对当前的进步至关重要。H使用同步加速器方法，Dr。 Almo的团队已经解决了人类蛋白质酪氨酸的结构问题 几种不同底物的复合体中的磷酸酶1B(PTP1B)， 使用在X9B收集的1.9A数据。PTP1B与a的络合物 合成法合成高亲和力非肽H底物 劳伦斯小组证明了一种新的芳基的存在 磷酸结合位点，为设计提供了一个新的H范式 紧密结合的抑制剂。这是报道的最高分辨率 这项工作最近发表在了 美国国家航空航天局。基于这些发现，劳伦斯实验室合成了一种 系列第二代双芳基PTP1B配体 磷酸盐官能团和数据已于 几个不同的复合体。

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.