Organic Chemistry

992 CHAPTER 23 Amino Acids, Peptides, and Proteins

The stabilizing interactions include covalent bonds, hydrogen bonds, electrostatic

attractions (attractions between opposite charges), and hydrophobic (van der

Waals) interactions. Stabilizing interactions can occur between peptide groups

(atoms in the backbone of the protein), between side-chain groups

and between peptide and side-chain groups. Because the side-chain groups help de-

termine how a protein folds, the tertiary structure of a protein is determined by its

primary structure.

Disulfide bonds are the only covalent bonds that can form when a protein folds. The

other bonding interactions that occur in folding are much weaker, but because there

are so many of them (Figure 23.12), they are the important interactions in determining

how a protein folds.

Most proteins exist in aqueous environments. Therefore, they tend to fold in a

way that exposes the maximum number of polar groups to the aqueous environ-

ment and that buries the nonpolar groups in the interior of the protein, away

from water.

The interactions between nonpolar groups are known as hydrophobic interac-

tions. These interactions increase the stability of a protein by increasing the entropy of

water molecules. Water molecules that surround nonpolar groups are highly

structured. When two nonpolar groups come together, the surface area in contact with

water decreases, decreasing the amount of structured water. Decreasing structure in-

creases entropy, which in turn decreases the free energy, which increases the stability

of the protein. (Recall that ¢G°=¢H°-T¢S°.)

(a-substituents),

Helical Structure

Pleated Sheet

Structure

COO−

H 3 N+

H

N

C

O

CH 2 OH O C

CHCH

(^2) CH
3
CH
3
CH
3
CH
3
CH
CH 2 C NH
H
OCH 2
H
(CH
(^2) )
(^4) NH
3

• OCCH−
  2
  O
  CH
  S
  S
  CH
  2
  O
  Figure 23.11
  Stabilizing interactions responsible for the tertiary structure of a protein.
  Max Perutzwas born in Austria in

1914. In 1936, because of the rise of
      Nazism, he moved to England. He
      received a Ph.D. from, and became a
      professor at, Cambridge University.
      He worked on the three-dimensional
      structure of hemoglobin and assigned
      the work on myoglobin (a smaller pro-
      tein) to John Kendrew (1917–1997).
      Kendrew was born in England
      and was educated at Cambridge
      University.

Max Ferdinand Perutzand John

Cowdery Kendrewwere the first to

determine the tertiary structure of a

protein. Using X-ray diffraction, they

determined the tertiary structure of

myoglobin (1957) and hemoglobin

(1959). For this work, they shared the

1962 Nobel Prize in chemistry.

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