Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold

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FIGURE 3-15 Rotation between planar peptide groups in proteins. Rotation about the Cα–amino nitrogen bond (the Φ angle) and the Cα–carbonyl carbon bond (the Ψ angle) permits polypeptide backbones, in principle, to adopt a very large number of potential conformations. However, steric restraints due to the structure of the polypeptide backbone and the properties of the amino acid side chains dramatically restrict the potential conformations that any given protein can assume.

A critical structural feature of polypeptides that limits how the chain can fold is the planar structure of the peptide bond. Figure 3-3 illustrates the amide group in peptide bonds in a polypeptide chain. Because the peptide bond itself behaves somewhat like a planar double bond (center and right),

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the portions of the polypeptide chain on either side of the peptide bond (P1 and P2) can be oriented in either a trans (center) or cis (right) configuration relative to the peptide bond. We saw similar cis and trans isomers of carbon-carbon double bonds in unsaturated fatty acids in Chapter 2. Analysis of crystal structures indicates that in proteins, about 99.97 percent of the peptide bonds that have any residue other than proline at P2 are in the trans configuration. (We will consider those with proline at P2 shortly.) In a peptide bond, the carbonyl carbon and amide nitrogen and those atoms directly bonded to them must all lie in a fixed plane (Figure 3-15); little rotation about the peptide bond itself is possible. As a consequence, the only flexibility in a polypeptide chain, allowing it to twist and turn—and thus fold into different three-dimensional shapes—is rotation of the fixed planes of adjacent peptide bonds with respect to one another about two bonds: the Cα–amino nitrogen bond (rotational angle called Φ) and the Cα–carbonyl carbon bond (rotational angle called Ψ).

Yet a further constraint on the potential conformations that a polypeptide chain can adopt is the fact that only a limited number of Φ and Ψ angles are possible because for most Φ and Ψ angles, the backbone or side-chain atoms would come too close to one another, and thus the associated conformation would be highly unstable or even physically impossible to achieve.