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Chemical Unfolding and Macromolecular Crowding of Alpha-1-Acid Glycoprotein

Shell, Elizabeth
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1115047649

Abstract Details

2005, PhD, University of Cincinnati, Arts and Sciences : Chemistry.
Alpha-1 acid glycoprotein (OMD) is an acute phase serum protein known to bind to various ligands. As a member of the lipocalin family, OMD has a tertiary structure of a beta-barrel core with alpha-helices external to the barrel core and two disulfide bonds. The structure of OMD is influenced by the environment which dictates its stability and ligand binding ability. OMD can have the disulfides reduced and the tertiary structure and binding site is affected by the oxidative state of the two disulfides. Reduction of the disulfides decreases stability and modifies the binding site of the protein to be more relaxed, perhaps even in a molten globular form. The reduced OMD is unable to bind to ligands such as warfarin in this state. Within the life of the protein, OMD is often crowded by other macromolecule. Cellular concentrations of macromolecules are between 30-40% and plasma concentrations are about 8%. Crowding with 10% (w/v) PEG leads to a decrease in the solvent accessible surface area of the protein, which increases the stability of OMD, since the unfolded state is disfavored. Crowding also changes the binding site of OMD and appears to be less accessible for the three tested ligands. The environment of the protein greatly influences the activity and shape of OMD. The different environments of the body can have a profound effect on OMD changing the pharmacological impact of this protein.
Brian Halsall (Advisor)
138 p.
Chemistry, Biochemistry
Macromolecular Crowding; Orosomucoid; Disulfides; Ligand

Recommended Citations

Citations

  • Shell, E. (2005). Chemical Unfolding and Macromolecular Crowding of Alpha-1-Acid Glycoprotein [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1115047649

    APA Style (7th edition)

  • Shell, Elizabeth. Chemical Unfolding and Macromolecular Crowding of Alpha-1-Acid Glycoprotein. 2005. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1115047649.

    MLA Style (8th edition)

  • Shell, Elizabeth. "Chemical Unfolding and Macromolecular Crowding of Alpha-1-Acid Glycoprotein." Doctoral dissertation, University of Cincinnati, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1115047649

    Chicago Manual of Style (17th edition)

ucin1115047649
434
© 2005, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.