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）：酶功能计划（EFI）将开发一个强大的基于序列/结构的策略，以促进在基因组计划中发现的未知酶的体外酶和体内代谢/生理功能的发现，这是基因组生物学的一个关键限制。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。