COLLABORATIVE CENTER FOR AN ENZYME FUNCTION INITIATIVE

酶功能倡议合作中心

• 批准号: 7901811
• 负责人: JOHN A GERLT
• 金额: $ 702.3万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-20 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901811
• 关键词: COLLABORATIVE; CENTER; ENZYME; FUNCTION; INITIATIVE

DESCRIPTION (provided by applicant): The Enzyme Function Initiative (EFI) will develop a robust sequence/structure-based strategy for facilitating discovery of in vitro enzymatic and in vivo metabolic/physiological functions of unknown enzymes discovered in genome projects, a crucial limitation in genomic biology. The EFI will accomplish this goal by integrating bioinformatics, structural biology, and computation with enzymology, genetics, and metabolomics. The EFI will establish five Scientific Cores for: 1) directing target selection as well as devising strategies for functional assignment based on sequence relationships and genome context; 2) expression and purification of targets; 3) experimental determination of structures of targets; 4) computational determination of structures of targets (homology modeling) and, also, in silico docking of ligand libraries to direct experimental assignment of in vitro functions by focused library screening; and 5) microbiological and metabolomic characterization of the in vivo roles of the in vitro assigned functions. The functional predictions will be tested by five Bridging Projects that focus on the functionally diverse amidohydrolase (AH), enolase (EN), glutathione transferase (GST), haloalkanoic acid dehalogenase (HAD), and isoprenoid synthase (IS) superfamilies. These superfamilies were selected because functional assignment cannot be accomplished by transfer of prior annotations based only on sequence or structural similarity: the reactions within each superfamily share conserved partial reactions but the identities of the substrates/products are not conserved. The EFI will disseminate to the scientific community the intellectual, computational, and experimental tools, protocols, materials, and guidelines for determining in vitro and in vivo functions of unknown enzymes. In achieving this goal, the EFI will nucleate and enable a larger consortium of investigators working toward the goal of realizing the biomedical potential of the vast amount of sequence data provided by genome projects.

描述（由申请人提供）：酶功能倡议（EFI）将开发出强大的序列/结构策略，以促进在基因组项目中发现的未知酶的体外酶和体内代谢/生理功能的发现，这是基因组项目，这是一种至关重要的限制。 EFI将通过将生物信息学，结构生物学和计算与酶学，遗传学和代谢组学相结合，来实现这一目标。 EFI将建立五个科学核心：1）基于序列关系和基因组环境的功能分配策略指导目标选择； 2）靶标表达和纯化； 3）实验确定目标结构； 4）计算确定目标结构（同源建模），以及在配体库的计算机对接中，以通过集中的库筛选来直接对体外功能进行实验分配； 5）体内分配功能的体内作用的微生物和代谢组表征。 功能预测将通过五个桥接项目进行测试，这些项目集中在功能多样的酰胺水解酶（AH），烯醇酶（EN），谷胱甘肽转移酶（GST），卤代酸脱脂酶（HAS）和异丙烯酸合酶（Isoprencrenoid synthase）（IS）超级元素中。之所以选择这些超家族，是因为仅通过基于序列或结构相似性的先前注释来转移功能分配：每个超家族内共享保守的部分反应中的反应，但底物/产物的身份并不保守。 EFI将传播科学界的智力，计算和实验工具，方案，材料和指南，以确定未知酶的体外和体内功能。在实现这一目标的过程中，EFI将构成和促进更大的研究人员，致力于实现基因组项目提供的大量序列数据的生物医学潜力。