Pharmacogenetics by Jeanne Ting Chowning

Molecular Modeling of Structures

Download the Cn3D software, if it is not already loaded on your computer. Cn3D is available at NCBI-Structure: http://pubmedexpress.nih.gov/Structure/CN3D/cn3d.shtml

Guanine and Thioguanine

  1. Go to http://www.ncbi.nlm.nih.gov/Structure and type 1N17 into the search box. After the search runs and an image appears, click on the image or on 1N17.

  2. Click STRUCTURE VIEW IN Cn3D, and then OPEN.

  3. When the structure opens, go to the STYLE menu and pick RENDERING SHORTCUTS → Ball and Stick.

  4. In the Sequence/Alignment Viewer window below the picture, click on a “g” (guanine) and watch it light up yellow in the structure.

  5. Back in the structure picture window, go to the SHOW menu and pick SELECTED RESIDUES. Everything except guanine should go away.

  6. Go to STYLE → COLORING SHORTCUTS → ELEMENT to show the different atoms. (You may need to click in the sequence/alignment viewer window to make the colors show again).

    • Guanine deoxynucleotied
      (with Oxygen circled)

    • Thioguanine deoxynucleotied
      (with Sulphur circled)

  7. Go to SHOW → Everything to see the whole DNA helix again.

  8. Repeat steps 4–6 above, but this time highlight the letter “n” in the Sequence/Alignment Viewer. That represents the Thioguanine. You should be able to see a yellow Sulphur atom attached where an Oxygen was in Guanine.

  9. Go to SHOW → Everything to see the whole DNA helix again.

  10. Go to STYLE → Rendering Shortcuts → Space fill. Now you can really see the impact of that Sulphur atom!

Human thiopurine S-methyltransferase (TPMT Enzyme)

  1. Go to http://www.ncbi.nlm.nih.gov/Structure and type 2BZG, into the search box.

  2. Click VIEW 3D STRUCTURE, and then OPEN. The parts represented in ball and stick form are the parts of the structure that vary depending on the allele.

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Originally published at http://www.sciencecases.org/pharmacogenetics/handout1.asp

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