Identify. Examine the following four amino acids (A–D):

What are their names, three-letter abbreviations, and one-letter symbols?

Properties. In reference to the amino acids shown in Problem 1, which are associated with the following characteristics?

Match ’em. Match each amino acid in the left-hand column with the appropriate side-chain type in the right-hand column.

Solubility. In each of the following pairs of amino acids, identify which amino acid would be more soluble in water: (a) Ala, Leu; (b) Tyr, Phe; (c) Ser, Ala; (d) Trp, His.

Bonding is good. Which of the following amino acids have R groups that have hydrogen-bonding potential? Ala, Gly, Ser, Phe, Glu, Tyr, Ile, and Thr.

Name those components. Examine the segment of a protein shown here.

Who’s charged? Draw the structure of the dipeptide Gly-His. What is the charge on the peptide at pH 5.5? pH 7.5?

Alphabet soup. How many different polypeptides of 50 amino acids in length can be made from the 20 common amino acids?

Sweet tooth, but calorie conscious. Aspartame (NutraSweet), an artificial sweetener, is a dipeptide composed of Asp-Phe in which the carboxyl terminus is modified by the attachment of a methyl group. Draw the structure of Aspartame at pH 7.

Vertebrate proteins? What is meant by the term polypeptide backbone?

Not a sidecar. Define the term side chain in the context of amino acid or protein structure.

One from many. Differentiate between amino acid composition and amino acid sequence.

Shape and dimension. (a) Tropomyosin, a 70-kDa muscle protein, is a two-stranded α-helical coiled coil. Estimate the length of the molecule. (b) Suppose that a 40-residue segment of a protein folds into a two-stranded antiparallel β structure with a 4-residue hairpin turn. What is the longest dimension of this motif?

Contrasting isomers. Poly-l-leucine in an organic solvent such as dioxane is α helical, whereas poly-l-isoleucine is not. Why do these amino acids with the same number and kinds of atoms have different helix-forming tendencies?

Exceptions to the rule. Ramachandran plots for two amino acids differ significantly from that shown in Figure 2.23. Which two, and why?

Active again. A mutation that changes an alanine residue in the interior of a protein to valine is found to lead to a loss of activity. However, activity is regained when a second mutation at a different position changes an isoleucine residue to glycine. How might this second mutation lead to a restoration of activity?

Exposure issues. Many of the loops on proteins are composed of hydrophilic amino acids. Why might this be the case?

Shuffle test. An enzyme that catalyzes disulfide–sulf-hydryl exchange reactions, called protein disulfide isomerase (PDI), has been isolated. PDI rapidly converts inactive scrambled ribonuclease into enzymatically active ribonuclease. In contrast, insulin is rapidly inactivated by PDI. What does this important observation imply about the relation between the amino acid sequence of insulin and its three-dimensional structure?

Stretching a target. A protease is an enzyme that catalyzes the hydrolysis of the peptide bonds of target proteins. How might a protease bind a target protein so that its main chain becomes fully extended in the vicinity of the vulnerable peptide bond?

Often irreplaceable. Glycine is a highly conserved amino acid residue in the evolution of proteins. Why?

Potential partners. Identify the groups in a protein that can form hydrogen bonds or electrostatic bonds with an arginine side chain at pH 7.

Permanent waves. The shape of hair is determined in part by the pattern of disulfide bonds in keratin, its major protein. How can curls be induced?

Location is everything 1. Most proteins have hydrophilic exteriors and hydrophobic interiors. Would you expect this structure to apply to proteins embedded in the hydrophobic interior of a membrane? Explain.

Location is everything 2. Proteins that span biological membranes often contain α helices. Given that the insides of membranes are highly hydrophobic (Section 12.2), predict what type of amino acids would be in such an α helix. Why is an α helix particularly suited to existence in the hydrophobic environment of the interior of a membrane?

Neighborhood peer pressure? Table 2.1 shows the typical pK_a values for ionizable groups in proteins. However, more than 500 pK_a values have been determined for individual groups in folded proteins. Account for this discrepancy.

Greasy patches. The α and β subunits of hemoglobin bear a remarkable structural similarity to myoglobin. However, in the subunits of hemoglobin, certain residues that are hydrophilic in myoglobin are hydrophobic. Why might this be the case?

Maybe size does matter. Osteogenesis imperfecta displays a wide range of symptoms, from mild to severe. On the basis of your knowledge of amino acid and collagen structure, propose a biochemical basis for the variety of symptoms.

Issues of stability. Proteins are quite stable. The lifetime of a peptide bond in aqueous solution is nearly 1000 years. However, the free energy of hydrolysis of proteins is negative and quite large. How can you account for the stability of the peptide bond in light of the fact that hydrolysis releases much energy?

Minor species. For an amino acid such as alanine, the major species in solution at pH 7 is the zwitterionic form. Assume a pK_a value of 8 for the amino group and a pK_a value of 3 for the carboxylic acid. Estimate the ratio of the concentration of the neutral amino acid species (with the carboxylic acid protonated and the amino group neutral) to that of the zwitterionic species at pH 7 (Section 1.3).

A matter of convention. All l amino acids have an S absolute configuration except l-cysteine, which has the R configuration. Explain why l-cysteine is designated as having the R absolute configuration.

Hidden message. Translate the following amino acid sequence into one-letter code: Glu-Leu-Val-Ile-Ser-Ile-Ser-Leu-Ile-Val-Ile-Asn-Gly-Ile-Asn-Leu-Ala-Ser-Val-Glu-Gly-Ala-Ser.

Who goes first? Would you expect Pro—X peptide bonds to tend to have cis conformations like those of X—Pro bonds? Why or why not?

Matching. For each of the amino acid derivatives shown here (A–E), find the matching set of ϕ and ψ values (a–e).

Scrambled ribonuclease. When performing his experiments on protein refolding, Christian Anfinsen obtained a quite different result when reduced ribonuclease was reoxidized while it was still in 8 M urea and the preparation was then dialyzed to remove the urea. Ribonuclease reoxidized in this way had only 1% of the enzymatic activity of the native protein. Why were the outcomes so different when reduced ribonuclease was reoxidized in the presence and absence of urea?