Principles of Biochemistry Volume 1 - A. Lehninger 1985

Biomolecules
Proteins: Covalent Structure and Biological Functions

Proteins (derived from the Greek word meaning "first" or "foremost") quantitatively outweigh all other macromolecules in living Cells, accounting for more than half of the dry weight of most organisms. In the previous chapter, we examined Amino Acids—the structural Building Blocks of proteins—and simple Peptides composed of a small number of amino acid residues linked together by peptide bonds. Now we turn our attention to Cell/13.html">Protein Structure, where molecules consist of very long polypeptide chains built from numerous amino acid units.

Proteins serve as the instruments through which Genetic information is actually realized. Given that the Cell Nucleus contains thousands of genes, each determining a specific trait of a living Organism, The Cell contains thousands of Different types of proteins, with each performing a specific function determined by its corresponding Gene. Thus, proteins are not only the most abundant macromolecules, but also exceptionally diverse in their Functions.

It is particularly striking that all proteins across all organisms, regardless of their function or biological activity, are constructed from the exact same basic set of 20 standard amino acids, each of which individually possesses no biological activity whatsoever. What, then, confers enzymatic activity on one protein, hormonal activity on another, and antibody properties on a third? How do proteins differ chemically? The answer is quite simple: proteins differ from one another because each possesses a unique, characteristic sequence of amino acid units. Amino acids are the alphabet of protein structure; by arranging them in various orders, it is possible to generate an almost infinite number of sequences and, consequently, an almost infinite variety of proteins (see Box 6–1).

Box 6–1. How Many Amino acid sequences Can Exist?

Every species of organism possesses thousands of different proteins, and the number of species itself is likely around 10 million. Is it possible to build, say, 10¹¹ (or more) different sequences using only 20 amino acids?

The answer is provided by pure mathematical calculation. A dipeptide composed of two different Amino acids can exist in two isomeric forms depending on their order. A tripeptide composed of three different amino acids—A, B, and C—can exist in six sequence-distinct variants: ABC, ACB, BAC, BCA, CAB, and CBA. The general expression for calculating the number of possible sequences for a row of distinct items is written as n! (read as "n factorial"), where n is the number of items. A tetrapeptide of four different amino acids can have 4! = 4 ∙ 3 ∙ 2 ∙ 1 = 24 different sequences. For a polypeptide of 20 different amino acids, none of which repeats twice, the number of sequences is 20! = 20∙19∙18..., yielding the astronomical figure of approximately 2∙10¹⁸. Yet this is a very short polypeptide, consisting of only 20 residues and having a Molecular Weight of about 2600. If we instead consider a protein with a molecular weight of 34,000, in which 12 different amino acids are present in equal proportions, the number of possible sequences is 10³⁰⁰. If we further assume this protein is built from 20 different amino acids in equal proportions, the number of possible sequences becomes vastly greater. If a single molecule of each of these possible isomers of such a protein were to exist, the combined weight of all these molecules would far exceed the weight of the Earth!

Thus, twenty amino acids can provide a sufficient number of sequences to account not only for the thousands of proteins present in every currently existing species, but also for the proteins of all species that ever existed in the past or will appear in the future. The species currently living on Earth are estimated to constitute roughly one-thousandth of all species that have ever inhabited our planet. The molecular logic of Amino Acids and Proteins amply accommodates the potential emergence of new species driven by the divergent nature of biological evolution.

In this chapter, we will examine the Introduction/19.html">Primary Structure of protein molecules, by which we mean the covalent backbone structure and The sequence of amino acid residues. We will also discuss certain relationships between Amino Acid Sequence and biological function.