Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2008
Lecture Notes: 22 September	© R. Paselk 2008
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3-D Structure of Proteins 3

Super Secondary structures (Motifs)

Recall the two classical structures based on the beta-strand seen above:

• Anti-parallel -pleated sheet: strong, linear H-bonds spaced adjacent, then R grp, then single, then R grp, then adjacent etc. (text Figure 4-6a)
• Parallel -sheet: evenly spaced, but slanted H-bonds (less stable, text Figure 4-6b)

Let's next look at some of the other more common motifs found in globular proteins:

• Hairpin - -strand-short loop--strand
• -meander - an anti-parallel beta sheet with short connecting loops
• motif - two successive alpha-helixes with slightly inclined axis to give better contact between side chains
• unit: alternate pattern of beta-strands and alpha-helixes (text Figure 4-17a)
• Greek Key
• -sandwich
• -barrel (text Figure 4-17b)

Tertiary Structures

The Tertiary structure describes the overall folding of a single covalent structure. With small proteins (< 200 aa residues) the overall structure is generally characterized by an overall tertiary folding with particular secondary structural segments to give particular motifs. Four small proteins are illustrated in your text:

• Myoglobin (text Figure 4-15) is a 153 residue globular protein in the globin family. Eight alpha helices form its single domain (myoglobin fold) tertiary structure; about 80% alpha helix (high for globular proteins). Interior almost exclusively hydrophobic residues, with water excluded from interior. Surface has mix of hydrophobic and hydrophilic residues, with ionizable groups on surface.
  • X-ray Diffraction determination of protein structure.
    • Review x-ray diffraction learned in Chem 109 (Bragg equation: n = 2d sin )
      
      
    • Note for proteins that each crystal point now becomes many points, each with its own "reflecting" plane.
    • Rotation to determine relative locations in three space results in thousands of reflections
    • Need to add heavy metals to act as "beacons" to locate positions in absolute space, and need to do a couple of times isomorphically (without altering the proteins structure - isomorphic replacements).

    Finally use Fourier transforms to convert angles and intensities of reflections to 3-D map of protein. (box 4-05 figure1)

  • NMR also capable of atomic resolution of protein structure (box 4-05 figure 2, 3)
    
  Myoglobin functions to store and facilitate the diffusion of oxygen in muscle. Oxygen binds to a heme {Fe (II)-protoporphyrin IX} prosthetic grp. Four of irons six ligands are to heme nitrogens, with a fifth to a histidine nitrogen. The final ligand bond goes to oxygen. Breathing motions (see below) are necessary to allow the exchange of oxygen, since the heme is in a closed pocket.
• Lysozyme (model)

Note that of the four, myoglobin, an intracellular protein, does not have dissulfide bonds, whereas the other three, all extracellular proteins, have dissulfide bonds to stabilize them in their relatively harsh environment.

Note also the presence of alpha-helices and beta-sheets in these proteins (text Table 4-2) to give motifs. -folding patterns, Figure 4-19.

• In looking at these motifs note that they tend to be made of layers allowing non-polar side chains to be buried so that hydrophobic forces stabilize them (text Figure 4-20a). Note that when -helices and -sheets occur together they are generally in different layers.
• Note that peptides segements nearby in the primary sequence generally stack adjacent to each other in the tertiary folded structure.
  • We also find that the folding follows relatively simple patterns, with no crossovers or knots. (text Figure 4-20b)
• -sheets are most stable, and thus most commonly found, when the individual segments have a slight right-handed twist. This leads to complex structures such as the -barrel etc. (text Figure 4-20d)

As the number of known protein structures increased, and larger proteins were determined, additional patterns became obvious within the tertiary level of structure: Motifs, which we introduced last time, & Domains.

Pathway Diagrams

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Last modified 23 September 2008