Skip to content
University of Maryland LibrariesDigital Repository at the University of Maryland
    • Login
    View Item 
    •   DRUM
    • Theses and Dissertations from UMD
    • UMD Theses and Dissertations
    • View Item
    •   DRUM
    • Theses and Dissertations from UMD
    • UMD Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    STRUCTURE FUNCTION DIVERSITY WITHIN THE PHOSPHOENOLPYRUVATE MUTASE / ISOCITRATE LYASE SUPERFAMILY AS REVEALED BY THE ENZYMES OXALOACETATE DECARBOXYLASE AND 2,3-DIMETHYLMALATE LYASE

    Thumbnail
    View/Open
    Narayanan_umd_0117E_10054.pdf (31.11Mb)
    No. of downloads: 449

    Date
    2008
    Author
    Narayanan, Buvaneswari Coimbatore
    Advisor
    Herzberg, Osnat
    Metadata
    Show full item record
    Abstract
    Two members of the phosphoenolpyruvate mutase (PEPM) / isocitrate lyase (ICL) superfamily were investigated to study their structure-function relationships and to identify sequence signatures that define a particular function. The first enzyme (PA4872) was a protein of unknown function from Pseudomonas aeruginosa. The second enzyme from Aspergillus niger (An07g08390) was thought to be an oxaloacetate acetyl hydrolase (OAH) because of its high sequence identity (~60%) to an enzyme with confirmed OAH activity. The X-ray crystal structure determination of PA4872 revealed unique features that guided the design of biochemical experiments, which ultimately led to the discovery that the enzyme is an oxaloacetate decarboxylase (OAD). Two structures of An07g08390, one with bound Mg2+ and the second with bound Mn2+ and the inhibitor 3,3-difluorooxaloacetate, were determined. The functional studies demonstrated that although the enzyme has OAH activity, it has a far better activity as a 2R,3S-dimethylmalate lyase (DMML). The active site structure of DMML indicated a proline residue (Pro240) as a marker of DMML function along with confirming the conserved locations of previously established signature residues for lyase activity. OAD is the founding member of a family within the PEPM / ICL superfamily and thus defines the function of the remaining family members. However, the biological context in which OAD functions remains unknown. DMML is known to function in the nicotinate catabolism pathway but not all the members of the pathway are present in A. niger. Transcriptome analysis suggests that the DMML encoding gene is under carbon catabolite repression but the pathway in which the enzyme functions has not yet been identified.
    URI
    http://hdl.handle.net/1903/9211
    Collections
    • Cell Biology & Molecular Genetics Theses and Dissertations
    • UMD Theses and Dissertations

    DRUM is brought to you by the University of Maryland Libraries
    University of Maryland, College Park, MD 20742-7011 (301)314-1328.
    Please send us your comments.
    Web Accessibility
     

     

    Browse

    All of DRUMCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister
    Pages
    About DRUMAbout Download Statistics

    DRUM is brought to you by the University of Maryland Libraries
    University of Maryland, College Park, MD 20742-7011 (301)314-1328.
    Please send us your comments.
    Web Accessibility