The Enzyme Function Initiative

    The Allen Laboratory is part of the Enzyme Function Initiative (EFI, http://enzymefunction.org/), partnering to develop a sequence/structure‑based strategy for discovery enzymatic functions of unknown enzymes discovered in genome projects. This information will address a major problem in genome biology in that functional assignment cannot be accomplished by transfer of prior annotations based only on sequence or structural similarity because often while the partial reactions are conserved, the identities of the substrates are not. This goal is being accomplished by integrating bioinformatics, structural biology, and computation with enzymology, genetics, and metabolomics. 

    The functional predictions will be tested in five bridging projects, one of which is the HAD superfamily, lead together by the Allen and Dunaway-Mariano laboratories. Functional assignment is based on sequence relationships and genome context, expression and purification of targets and screening of substrate libraries which are selected by the experimental determination of “dockable” structures of targets and in silico docking of ligand libraries. Microbiological and metabolomic characterization are used to assess the in vivo roles of the in vitro assigned functions.