The Peptide Bond

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Protein Structure
Proteins consist of one or more strings of amino acids joined end-to-end to produce a polypeptide. The characteristics of each protein are due to the different amino acids that are combined to make the polpeptide(s). Each of the 20 or so common amino acids has a different side chain but the basic structure is common to all amino acids.

Amino acids have a central α-carbon atom, a carboxylate group (—COO^⊖), and an amino group (—NH₃^⊕). The fourth group attached to the α-carbon is the side chain (The third group is —H). Side chains can be as simple as —H (= glycine), or —CH3 (= alanine). In the example shown on the right, the side chain is —CH₂OH (= serine).

Proteins are synthesized by the translation machinery consisting of ribosomes , aminoacyl-tRNAs, and various translation factors. The template for synthesis is messenger RNA (mRNA) copied from the gene. Amino acids are strung together in a particular order specified by the mRNA codons.

The biosynthesis reaction is complex. It is coupled to hydrolysis of at least three ATP equivalents because the joining of two amino acids is thermodynamically unfavorable. The actual chain elongation reaction is catalyzed by the peptidyl transferase activity of the ribosome. The new bond that is created is called a peptide bond.


In the reaction shown above, the carboxylate group of the amino acid alanine is joined to the amino group of the amino acid serine to create a dipeptide with a peptide bond. Water is eliminated in this reaction. During protein synthesis the reaction continues as the mRNA is translated and long strings of several hundred amino acid residues are made.

The peptide bond has some interesting properties that play an important role in determining the three-dimensional structure of proteins. Look at the traditional depiction of the peptide bond in part (a) (top) of the figure on the left. It shows the actual peptide bond as a single bond and the bond between the carbon atom and the oxygen atom as a double bond. Note that the nitrogen atom has a pair of unshared electrons represented by the two red dots.

The middle structure shows that one electron from the nitrogen and carbon atoms can redistribute to form a double bond between C and N. This leaves an unshared pair of electrons on the oxygen atom. The actual bonding pattern is a mixture of these two resonance forms as shown in the bottom structure.

The partial double bond nature of the peptide bond has important consequences since it inhibits rotation around this bond. With a single bond there is free rotation so the groups on either side can adopt many different conformations. With a double bond there is very little rotation and the groups on either side are locked into the conformation that was formed when the bond is created.

The peptide bond has enough of a double bond characteristic to prevent rotation of the two newly joined amino acid residues. Thus, the O—C—N—H atoms around the peptide bond lie in a single plane shown in blue in the figure on the right.

What this means is the polypeptide chain is somewhat stiff and rigid. It can only adopt conformations that result from rotation around the other bonds in the chain. There are only two of these other bonds that can rotate. Looking at the central α₂ carbon atom above, you can see that there can be rotation around the N—C_α bond and around the C_α—C bond.

The angle of rotation around the N—C_α bond is called Φ (phi) and the angle around the C_α—C bond is called Ψ (psi). For each pair of amino acid residues, these two angles are all that's needed to specify the three-dimensional shape of the polypeptide backbone of the protein.

Not all angles are possible as shown on the left. If the two negatively charged oxygen atoms are too close together they will repel one another. This clash is called steric hindrance and it further limits the number of possible conformations of the polypeptide chain.

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