Each ionizable group of an amino acid can exist in one of two states, charged or neutral. The electric charge on the functional group is determined by the relationship between the group’s pK_a and the pH of the solution. This relationship is described by the Henderson-Hasselbalch equation (discussed in Chapter 3).

A quantitative amino acid analysis reveals that bovine serum albumin (BSA) contains 0.58% tryptophan (M_r 204) by weight.

A peptide has the following sequence:

E–H–W–S–G–G–L–R–P–G

A biochemist isolates a peptide hormone with the following sequence:

ADSERNCQLVILLAWLPGVKVQCALLDRET

The sequence shown below, with 86 amino acid residues, folds into a β sheet substructure within a protein. The residues that form the β strands are noted (by residue number) above the sequence, and those outside the sheet are shown below. What type of β sheet structure is likely to form, parallel or antiparallel? Explain. What types of secondary structure are possible in the sequences between the β strands?

Given that the β strands in the β sheet structure of Problem 5 contain hydrophobic residues in most of the even-numbered positions and that most of the odd-numbered residues have polar R groups, predict how the β sheet structure will fold in three dimensions.

Ramachandran plots can help increase the accuracy of models derived from x-ray crystallography data. The plot below was created by measuring ψ and φ for each amino acid residue in a 2.2 Å resolution crystal structure. In the plot, which excludes Gly and Pro residues, selected residues (dots) are numbered 1 through 5. What types of secondary structure are most consistent with the location of each of the numbered residues? Which residue(s) would you suspect of being incorrectly modeled into the electron density map? How would your suspicions change if the plot had included Gly residues?

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Inspect the 20-residue sequence below and predict the most favorable region for an α helix that is 10 residues long. Explain your reasoning. Point out any stabilizing interactions that might occur.

AIPRKKREFICRFGAIRPNT

Predict which of the following sequences would bind ATP (or GTP), and explain your answer. (See the How We Know section in this chapter.)

A polypeptide chain has 140 amino acid residues. How long will the polypeptide chain be if it is entirely α-helical? How long will it be if it is one continuous β strand?

Compare and contrast four aspects of the use of NMR and x-ray crystallography in protein structure determination.

Five proteins are listed below, each a monomer containing the number of amino acid residues indicated. How many domains would you expect each protein to have? Explain your reasoning.

For the following 20-residue sequence in a protein, list five amino acid residues that are likely to be buried in the protein, inaccessible to water. Pick five that are good candidates for surface residues.

DLKFTISVGAPVLTREQLLE

Consider an α helix in isolation, apart from the rest of the protein:

NRGAAEGAFCRAN

How would the following amino acid substitutions (indicated by residue number) affect the stability of the helix?

A simple protein structure is shown below, from two different angles. In (a), label the N-terminus and C-terminus and the two β turns. In (b), indicate which side of the β sheet, left or right, is likely to be more hydrophobic.

Draw a topology diagram for a 10-stranded, up-and-down β barrel.

Three Ramachandran plots are shown below. One of these is a guide; the other two, (a) and (b), are plots for two proteins, also shown below. Match each Ramachandran plot with its protein: which plot is most likely to be derived from bovine serum albumin, and which from green fluorescent protein? Both plots were downloaded from the Protein Data Bank. They are drawn a bit differently, but the axes are the same as in the guide.

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When proteins are synthesized in cells, all of the peptide bonds are synthesized in the trans configuration. Some proteins, however, have peptide bonds—especially adjacent to Pro residues—that are in the cis configuration. How do the peptide bonds in the cis configuration arise?

Food for thought: In this chapter, we introduce quaternary structure as the assembly of multiple protein subunits. This assembly is generally enforced through weak, noncovalent interactions—mainly the hydrophobic effect. Later in this book, we will deal with many very large multimeric complexes. For example, the ribosomes that are responsible for protein synthesis in all cells are assemblies of dozens of proteins and multiple large RNA molecules, with aggregate molecular weights in the millions. Are weak, noncovalent interactions sufficient to keep such complexes together?