Protein Chemistry. Structure, Properties, Research Methods - Shendryk A.N. 2022

Protein Structure
Spatial Structure of Proteins
Structural Role of the Peptide Bond - Geometric Parameters of the Peptide Bond

In the Cells of living organisms and plants, Amino Acids are incorporated into polypeptide chains via complex biochemical reactions. This "polymerization" is The process of forming amide (peptide bonds). The chain direction is defined from the N-terminal to the C-terminal amino acid.

It is precisely in this sequence that the synthesis of protein peptide chains proceeds in vivo. This direction corresponds to the 5’→3’ direction of Messenger RNA.

Almost all our knowledge regarding the spatial arrangement of atoms in Proteins is based on X-Ray Diffraction (XRD) analysis of simple Peptides conducted by Pauling and Corey in the early 1950s. The results of these and subsequent studies established the fundamental geometric parameters of peptide bonds, which are summarized below.

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Key Structural Features of the peptide bond.

1. The four atoms of the peptide group lie in the same plane as the a-carbon atoms. The H and R-group atoms attached to the a-carbon atoms lie outside this plane, see figure.

2. The O and H atoms of the peptide bond typically exhibit a trans-orientation. The two a-carbon atoms also adopt a trans-orientation relative to the peptide bond that connects them. The peptide bond is essentially planar (the sum of the Bond Angles at the C and N atoms is close to 360∘).

3. When all amino acids incorporated into the peptide chain are in the L-conformation, the R-groups at each a-carbon atom are arranged regularly in a trans position relative to one another.

4. The C-N bond length in the amide group (i.e., in the peptide bond) is 1.32 Å, which is intermediate between a double covalent bond (1.21 Å) and a single covalent bond (1.47 Å). Consequently, the C-N bond possesses a partial double (π) bond character.

5. The C=O bond is 0.02 Å longer than the C=O bond in aldehydes and ketones. Pauling and Corey explained these findings through the Resonance of the following structures:

Structure (I) is compatible with free rotation around the C-N bond, whereas such rotation is restricted for structure (II). Judging by the differences in the C’-N and C’-O Bond Lengths, the resulting hybrid structure can be represented as comprising forms (I) and (II) in a 3:2 ratio. In other words, the C’-N bond has a 40% double-bond character. Since structure (II) is planar while structure (I) allows free rotation, the hybrid structure must also be planar.

6. Each planar peptide unit contains two bonds to the a-carbon atoms around which free rotation is permitted. Both are σ-bonds lacking any significant π-contribution. These are the C^a-N and C^a-C bonds. The corresponding angles of rotation (dihedral angles) are designated as: φ for C-N and ψ for C^a-C. For a fully extended chain, the angles φ and ψ are considered equal to 0∘, and when viewed from the N-terminus, a clockwise rotation of 180∘ is assigned a "+" sign, while the opposite direction is assigned a "-" sign, see figure:

The peptide group in native proteins generally adopts a trans-conformation. However, in strained cyclic systems (such as certain cyclopeptide derivatives of Proline) as well as in N-alkylated derivatives with bulky substituents on the nitrogen atom, the peptide group may occur in the cis-form. For example, a single cis-peptide group is found in subtilisin preceding Pro-168, two in Ribonuclease S preceding Pro-93 and Pro-114, and one in Carboxypeptidase A between Ser-197 and Tyr-198, etc. Among all amino acids, Pro has the highest propensity to promote cis-conformation formation.