HIGH RESOLUTION CRYSTALLOGRAPHY OF HEME ENZYMES WITH SUBSTRATE-LINKED SENSITIZER

具有底物连接敏化剂的血红素酶的高分辨率晶体学

• 批准号: 7370385
• 负责人: DAVID B. GOODIN
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370385
• 关键词: RESOLUTION; CRYSTALLOGRAPHY; HEME; ENZYMES; SUBSTRATE

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. Currently there is substantial interest in the substrate access pathway and the conformational changes associated with substrate binding to P450s. To fully analyze these specific interactions, substrate-linked sensitizer (SLS) probes have been developed. To date, 1.55 and 1.65 ¿¿structures of ruthenium tris-bipyridyl probes bound to P450cam have been solved, along with 2.2, 1.8, and 1.45 ¿¿structures of fluorescent-based probes bound to P450cam. As the design process continues to optimize the SLS probes for spectroscopic studies and inhibitor identification, alternative fluorophores will be explored in a second generation of probes. Thus, the high-resolution crystallographic studies in this proposal will significantly aid in the long-term goal of developing enzyme-specific probes for analyzing the complex mechanisms of molecular recognition as well as for rapid screening of inhibitors of bio-medically important enzymes such as cytochrome P450s.

该主题项目是利用NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是针对该中心的，这不是调查人员的机构。当前，对底物访问途径以及与底物与P450的结合相关的构象变化引起了极大的兴趣。为了充分分析这些特定的相互作用，已经开发了底物连接传感器（SLS）问题。迄今为止，已解决了与P450CAM结合的ruthenium tris-Bipyridyl探针的结构，以及2.2、1.8和1.45€«基于P450CAM的荧光问题结构的结构。随着设计过程继续优化光谱研究和抑制剂鉴定的SLS问题，第二代问题将探索替代性荧光团。这是该提案中的高分辨率晶体学研究将显着有助于开发酶特异性问题的长期目标，以分析分子识别的复杂机制，以及快速筛选生物形成重要重要酶的抑制剂，例如细胞色素P450。