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Structural Analysis of 5'-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Helicobacter pylori for the Purpose of Drug Development

Iacopelli, Natalie Marie
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1249666505

Abstract Details

2009, Master of Science, University of Toledo, Chemistry.
5’-Methylthioadenosine (MTA)/S-Adenosylhomocysteine (SAH) nucleosidase isan essential enzyme for all bacteria. It is involved in many cellular processes including: polyamine synthesis, quorum sensing, methionine metabolism, and biological methylation. 1-4 Because of the essential nature of this enzyme, MTA/SAH nucleosidase is a viable broad-spectrum antibiotic target. The gene encoding for MTA/SAH nucleosidase from Helicobacter pylori was cloned, expressed, and purified using immobilized metal affinity and size exclusion chromatography. The purified MTA/SAH nucleosidase was crystallized in native form then subjected to X-ray diffraction studies and structurally analyzed using macromolecular X-ray crystallography. MTA/SAH nucleosidase was also crystallized in two additional states: one bound to a substrate analog (Formycin-A), and one with adenine. Analysis of the three structures supports previously theorized catalytic mechanisms and models. 5,6 Also, the presence of a Tris molecule within the active site of the native and adenine-bound structures provides insight into the development of a Tris-based enzyme inhibitor.
Donald Ronning, PhD (Advisor)
Timothy Mueser, PhD (Committee Member)
Max Funk, PhD (Committee Member)
133 p.
Biochemistry
5'-Methylthioadenosine; S-Adenosylhomocysteine; Nucleosidase

Recommended Citations

Citations

  • Iacopelli, N. M. (2009). Structural Analysis of 5'-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Helicobacter pylori for the Purpose of Drug Development [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1249666505

    APA Style (7th edition)

  • Iacopelli, Natalie. Structural Analysis of 5'-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Helicobacter pylori for the Purpose of Drug Development. 2009. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1249666505.

    MLA Style (8th edition)

  • Iacopelli, Natalie. "Structural Analysis of 5'-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Helicobacter pylori for the Purpose of Drug Development." Master's thesis, University of Toledo, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1249666505

    Chicago Manual of Style (17th edition)

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© 2009, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.