KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Metalloproteins: Structure Determination (HADH), Inhibition (P4H), and Biomimetic Systems (P-1[Ru(NO)(Cl)])

    Thumbnail
    View/Open
    Reed_ku_0099D_10055_DATA_1.pdf (31.21Mb)
    Issue Date
    2008-01-01
    Author
    Reed, Timothy M.
    Publisher
    University of Kansas
    Format
    227 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    Histamine dehydrogenase from Nocardioides simplex (HADH) is a flavoprotein that converts histamine to imidazole acetaldehyde and is highly specific for histamine. Chapter one describes the development of overexpression and purification a recombinant form of HADH (rHADH) and its basic biochemical characterization. Chapter two describes X-ray structure determination of rHADH. Diffraction data were collected to 2.7 Å resolution with 99.7% completeness. The histamine binding motif of HADH are very similar to those in the other histamine binding proteins. Prolyl-4-hydroxylase (P4H) belongs to a family of αketoglutarate-dependent non-heme iron oxygenases. Selective inhibitors of P4H can be potential therapeutics for fibrosis. Chapter three discusses the design of inhibitors that target P4H in the ER using the signal peptide KDEL, which is specific to the ER. Phenanthroline-GKDEL demonstrates a 100-fold increase in potency in inhibiting P4H produced in the cultured human fibroblast cells versus isolated enzyme. Fluorescent microscopy using a fluorescently tagged inhibitor demonstrates uptake of the phen-E(EDANS)VKDEL inhibitor into the ER. Nitric oxide (NO) is an important signaling molecule in the body, and the site-specific timed release NO could be utilized in the treatment of various medical conditions. Chapter four discusses the photorelease of NO from a ruthenium salen complex immobilized within a porous material. This material transfers NO to myoglobin within 20 minutes. NO is released from this material in the presence of light; however, during periods of darkness, the release of NO was not observed. This is the first system where NO is photoreleased from an immobilized polymer support.
    URI
    http://hdl.handle.net/1808/4562
    Collections
    • Dissertations [4473]
    • Chemistry Dissertations and Theses [336]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps