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Gale Rhodes
Chemistry Department
University of Southern Maine

Revised 2006/08/02

Learn how to use Swiss-PdbViewer: Work through sections 1-4 of the Swiss-PdbViewer Tutorial.

Topic: Nucleotides and Nucleic Acids

Several important cofactors and prosthetic groups are, or contain, nucleotides. Nucleotides are the building blocks of nucleic acids. Use this page to take a closer look at their structures.

Examples

I. Nucleotide Coenzymes

Following are brief descriptions of some important nucleotides or nucleotide-containing molecules, along with links to structure files for viewing with Swiss-PdbViewer or your favorite viewer. As you view each structure, try to identify all of the components and bonding groups mentioned in the description.

NOTE: Most of these structure files are derived from crystallographic structures of proteins carrying these molecules. In most cases, crystallographic images are not sharp enough to reveal hydrogen atoms. Therefore, hydrogens are missing from most of these files. A biochemist's knowledge of organic chemistry tells her or him where the hydrogens are located. You will quickly become accustomed to seeing biological structures without the hydrogens.

(The title of this section is Nucleotide Coenzymes. Which of the following are better described as coenzymes, cofactors, cosubstrates, or prosthetic groups?)

  1. ATP, or adenosine triphosphate, a nucleotide triphosphate composed of adenine joined by its N-9 to C-1' of ribose by a beta linkage, with a triphosphate group on C-5' of the ribose. As you will learn later, the triphosphate group of ATP takes part in phosphate-group-transfer reactions. From PDB file 1KAX.
  2. NAD, or nicotinamide adenine dinucleotide, is composed of nucleosides of nicotinamide and adenine joined at their C-5' positions by a diphosphate group. The nicotinamide portion of NAD takes part in oxidation and reduction reactions. From PDB file 1UDB.
  3. FAD, or flavin adenine dinucleotide, is composed of adenosine and a nucleoside containing riboflavin and the sugar alcohol ribotol. As in NAD, the two nucleosides are joined by a diphosphate link between their 5' carbons. Riboflavin, like nicotinamide, takes part in oxidation and reduction reactions. From PDB file 1BV4.
  4. Many cofactors (including the previous three) contain AMP, but not always with other nucleosides. An example is CoA, coenzyme A, in which pantothenic acid and beta-mercaptoethylamine are joined sequentially to the second phosphate group of ADP. The sulfhydryl group of coenzyme A often carries acyl groups, joined by a thioester link, during a variety of metabolic processes. In this example, CoA is joined by a thioester link to the pamitolyl group, CH3(CH2)14CO, shown in green. You can select and display CoA or the pamitoyl group separately. This molecule is shown as found in acyl-CoA-binding protein from E. coli (PDB file 1ACA). The structure was determined by NMR spectroscopy, so hydrogens are shown.

II. Nucleic Acids

Three Conformations of DNA

Following are links to structure files of the three most common DNA conformations. After downloading each one, calculate H-bonds to see base-pair bonding between the chains. Find AT and GC pairs from the hydrogen-bonding patterns. Find the major and minor grooves in each conformation. Which models are right-handed helices and which are left-handed helices?

  1. B-DNA Probably the most common DNA conformation in cells.
  2. A-DNA A dehydrated form of DNA, probably not very common in cells. However, double-stranded RNA and DNA/RNA duplexes are sometimes found in this conformation.
  3. Z-DNA An unusual DNA conformation found in the crystalline structure of certain synthetic DNAs. It is not clear whether Z-DNA has any biological function..

How Do We Know DNA Structure?

DNA structure was first revealed by analysis of x-ray diffraction by DNA fibers.

  1. Slide 1: Fiber diffraction experiment.
  2. Slide 2: Relationship between molecular dimensions and diffraction pattern.
  3. Slide 3: Diffraction by fibers of A- and B-DNA.

Example of Intercalation Compound

  • DNA-Daunamycin Complex: This model is an example of how molecules called intercalators can bind to DNA. Intercalators slip in between the bases and stretch the DNA slightly. This distortion of the shape of the double helix can block replication or result in mistakes in replication (mutations).

III. DNA-Protein Complexes (For Advanced Deep View Users)

Work through sections 1-6, 10, and 11 of the tutorial before doing this exercise. Also, because water molecules are often important participants in protein-DNA interactions, configure Deep View to load and display water, as follows:

  1. Start Deep View and click Cancel on the initial file-open dialog.
  2. Prefs: Loading Proteins
  3. Check Show Solvent (if loaded), and uncheck Ignore solvent (WAT SOL HOH).

DNA-Eco RI Complex

Download this Deep View project file containing a model of the restriction enzyme Eco RI complexed to its target DNA. Superimposed on the DNA is a model of B-DNA. Comparison of the two DNA models reveals conformational changes forced on the DNA when Eco RI binds. Study these models as you read about this protein-DNA complex in your text or web sources. Use blinking (hold down control, then press tab) to turn the models on and off in succession.

Studying Other Protein/Nucleic-Acid Complexes

You can use the B-DNA model from Section I above to make similar displays for other DNA-binding proteins.

  1. Open a DNA-protein model from the PDB.
  2. Open the B-DNA model from Section I.
  3. Display only the B-DNA and the DNA from the DNA-protein model. Display only the backbones.
  4. Using the Layer Infos window to control movement, superimpose the backbone of the B-DNA model onto the backbone of the other DNA.
  5. Blink between the models to reveal the extent of conformational change that the protein forces upon the DNA.
  6. Add the protein to reveal specific interactions in protein-DNA binding.
  7. Use the model to help you understand more about the discussion of this complex in your text.
  8. If the bound DNA looks a lot like A-DNA (Section I), try the same operations with the A-DNA model.

If you make any such displays, please share them with me by attaching them to email.

Download this Deep View Project file containing seven DNA-binding proteins, each in complex with its cognate or target DNA. In all models, the DNA is roughly superimposed on layer #1, a dodecamer of B-DNA. The layers in this model are listed below, with links to the PDB entry for each model, to allow you to learn more about the models -- recall that Deep View project files do not contain the header information for each PDB file included. These models sample a wide range of variety of DNA-binding protein types. Read about each one in your biochemistry text as you explore it.

  1. B-DNA dodecamer (PDB 2BNA)
  2. 434 phage repressor, type: helix-turn-helix (PDB 2OR1)
  3. E. coli trp repressor, type: helix-turn-helix, indirect readout (PDB 1TRO)
  4. E. coli met repressor with co-repressor, type: two-strand antiparallel beta sheet (PDB 1CMA)
  5. Mouse Zif268 gene regulator protein, type: mononuclear zinc finger (PDB 1ZAA)
  6. Yeast GAL4 transcription activator, type: binuclear zinc finger (PDB 1D66)
  7. Mouse Max transcription factor, type helix-loop-helix with leucine zipper (PDB 1AN2)
  8. Yeast GCN4 transcription activator, type: leucine zipper (PDB 1YSA)

Here are some questions you can answer for each model by exploring with Deep View:

  1. Find the structural element that characterizes this particular type of DNA-binding protein.
  2. Find sequence-specific interactions between protein and DNA bases.
  3. Find non-specific interactions between protein and sugars or phosphates.
  4. Find interactions that are mediated by water molecules.
  5. Does the protein interact with DNA in the major groove or the minor groove?
  6. Characterize specific interactions as ionic, H-bond, polar, or nonpolar.
  7. Does the protein distort the DNA double helix?
  8. Is the recognition site on DNA palindromic? If so, does protein symmetry reflect sequence symmetry?

Topics List

Biochemistry Resources