PHYSICAL/CHEMICAL TRAPPING & LAUE DIFFRACTION/TIME-RESOLVED CRYSTALLOGRAPHY O

物理/化学捕获

• 批准号: 7725987
• 负责人: DAHUI LIU
• 金额: $ 1.19万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725987
• 关键词: Active Sites; Aspartate Transaminase; Biochemical Reaction; Catalysis; Chemicals; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Development; Disease; Drug Delivery Systems; Drug Design; Elastases; Enzymatic Biochemistry; Enzymes; Funding; Grant; Imagery; Institution; Ligands; Liquid substance; Methods; Nature; Numbers; Pancreatic Elastase; Pharmaceutical Preparations; Protein Dynamics; Protein Engineering; Research; Research Personnel; Resources; Source; Staging; Structure; System; Time; United States National Institutes of Health; abstracting; analog; design; enzyme mechanism; enzyme model; enzyme substrate; homoserine lactone; inhibitor/antagonist; mimetics; mimicry; novel; tool

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. Abstract: The visualization of enzymes trapped in various stages of catalysis has been invaluable in understanding the catalytic mechanisms of enzymes and has been used successfully as a tool for rational drug design. Mimicry of a substrate and its transformed structures during catalysis is an effective means to design inhibitors and drugs. Indeed, a great number of drugs are mimetic analogs of the target enzyme?s substrates, products, intermediates, or transition state. Direct observation of the productive substrate complexes has also provided valuable information about protein dynamics. An enzymatic reaction is a fluid continuum of structural changes of both the enzyme and its ligands. Recent developments in enzymology, protein engineering, and rational drug design demand dynamic structural information to understand the whole continuum of an enzymatic reaction and to broaden the potential targets of drugs. We propose to use three diseases-related enzyme models, elastase, N-acyl homoserine lactone hydrolas, and aspartate aminotransferase to explore the structural dynamics of enzyme catalysis in hope of leading to novel drug design. We plan to use different chemical/physical trapping methods to capture the transient structural natures of enzyme active sites. Furthermore, we would like to make our best effort to develop a time-resolved system to study enzymatic reactions in general.

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