Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Proteins
Primary structure of proteins

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Fig. 6.1. The twenty most frequently occurring side chains.

Proteins represent one of the Major Classes of biological macromolecules. The wide range of Functions they perform is reflected in the immense diversity of their chemical structures and spatial Conformations. Globular proteins, which can be roughly approximated as spheres, are involved in specific processes such as catalysis (Chapters 12, 13, 14), transport (Chapter 15), or regulation (Chapter 28). Fibrous proteins (Chapter 11), such as Collagen, Keratins, and Silk Fibroin, are highly elongated and frequently serve a structural role due to their inherent elasticity or rigidity.

Four Levels of Protein structural Organization

Proteins are commonly described using the terms primary, secondary, tertiary, and quaternary Structure. Primary Structure refers to the chemical formula of a protein, represented as a linear sequence of amino acid residues. The terms secondary, tertiary, and quaternary structure denote the various levels of Spatial Organization of this linear sequence (Chapters 9, 10).

Amino acid residues, linked sequentially to one another, are the primary components of proteins. Each residue features a constant part (i.e., identical across all residues) and, with the exception of the two terminal residues, is bonded to two others in such a way as to form a continuous, unbranched chain known as the polypeptide backbone. Attached to each alpha-carbon (C^α) atom of the backbone are the variable parts of The amino acid residues (side chains, or R groups). Proteins typically contain 20 different R groups.

A free amino acid differs from an amino acid residue by the presence of an additional hydrogen atom at one end (and consequently an —NH₂ amino group) and an additional hydroxyl group (—OH) at the other end (and consequently a —COOH, or carboxyl group) (Fig. 6.2).

A peptide bond is formed via a Condensation reaction between the amino group of one free Amino Acid and the carboxyl group of another (or between the amino group of a free amino acid and the carboxyl terminus of a polypeptide), with the release of Water. Thus, free Amino Acids serve as the monomers from which a polymer—the protein molecule—is built through polycondensation. The polypeptide chain is synthesized via repeating cycles of peptide bond formation.

One end of the chain terminates in a free —NH₂ group (the N-terminus), while the other terminates in a free —COOH group (the C-terminus).

The Amino Acid Sequence is the order in which residues are arranged along the polypeptide chain. Protein molecules typically contain 40 or more residues, although Polypeptides consisting of 1,000 or more residues are also known. This high sequence Variability provides the vast diversity of protein structures and functions. Because polypeptides are constructed primarily from 20 different amino acids, a protein containing 100 residues has 20¹⁰⁰ (i.e., approximately 10¹³⁰) possible sequence variants. The Classification of side chains is based on differences in their properties under normal physiological conditions, i.e., at a pH of approximately 7. Polar negatively charged residues—Asp⁻ and Glu⁻—contain a negatively charged COO⁻ group. In their COOH (i.e., protonated) form, they can act as acids. Polar positively charged residues—Arg⁺, His⁺, and Lys⁺—carry a positive charge due to the protonation of a nitrogen atom. In their deprotonated form, they can exhibit basic properties. Polar uncharged residues—Asn, Gln, Ser, and Thr—possess polarized covalent bonds and, consequently, electronegative and electropositive regions. Nonpolar, or hydrophobic, residues—Ala, Cys, Ile, Leu, Met, Phe, Pro, Trp, Tyr, and Val—contain bulky aliphatic or aromatic hydrocarbon chains. The hydrophobic properties of Cys, Trp, and Tyr are slightly diminished by the presence of polar groups (—SH, >NH, and —OH, respectively). Neutral residues are represented solely by Gly, whose side chain is a single hydrogen atom.

Fig. 6.2.

A disulfide bond (or disulfide bridge) is a covalent linkage connecting either two PARTS OF THE same polypeptide chain or two different polypeptides. Disulfide Bonds are formed by The oxidation of two Cysteine residues (i.e., the removal of hydrogen from two reactive sulfhydryl —SH groups). The resulting new residue is called cystine.

Proline is an unusual residue because one end of its side chain is covalently bonded to the C^α atom and the other to the N atom of the backbone within the same residue, forming a ring structure.

Stereoisomerism is characteristic of all amino acids except Gly. The C^α atom is asymmetric because it is bonded to four different chemical groups. Consequently, two possible configurations exist for each amino acid, known as D and L forms (also referred to as enantiomers or stereoisomers). A solution of one stereoisomer rotates the plane of polarized light in one direction, while a solution of the other rotates it in the opposite direction—a phenomenon known as optical activity. Only L-isomers are found in proteins. To distinguish between the D and L configurations, one looks along the bond from the hydrogen atom toward the C^α atom and "reads" the three remaining groups attached to C^α in a clockwise direction: for the L-form, the groups CO, R, and N spell the word CORN. The side chains of Thr and Ile feature an additional optical center—the beta-carbon atom bonded to the alpha-carbon of the backbone.

Fig. 6.3.

Fig. 6.4.