Polypeptides

The chain formed by polymerization of amino acid molecules provides the primary structure of a protein. Together with any covalent crosslinkages and other modifications, this may also be called the covalent structure of the protein. Each monomer unit in the chain is known as an amino acid residue. This term acknowledges the fact that each amino acid has lost one molecule of H2O during polymerization. To be more precise, the number of water molecules lost is one less than the number of residues. Peptides are named according to the amino acid residues present and beginning with the one bearing the terminal amino group. Thus, L-alanyl-L-valyl-L-methionine has the following structure:


Like amino acids, this tripeptide is a dipolar ion. The same structure can be abbreviated Ala-Val-Met or, using one-letter abbreviations, AVM. It is customary in describing amino acid sequences to place the aminoterminal (N-terminal) residue at the left end and the carboxyl-terminal (C-terminal) residue at the right end. Residues are numbered sequentially with the N-terminal residue as 1.
The sequence of amino acid units in a protein is always specified by a gene. The sequence determines how the polypeptide chain folds and how the folded protein functions. For this reason much effort has gone into “sequencing,” the determination of the precise order of amino acid residues in a protein. Sequences of several hundreds of thousands of proteins and smaller peptides have been established and the number doubles each year.

(A) The complete amino acid sequence of the cytoplasmic enzyme aspartate aminotransferase from pig heart. The peptide has the composition Lys19, His8, Arg26, (Asp + Asn)42, Ser26, Thr26, (Glu + Gln)41, Pro24, Gly28, Ala32, Cys5, Val29, Met6, Ile19, Leu38, Tyr12, Phe23, Trp9. The molecular mass is 46.344 kDa and the complete enzyme is a 93.147-kDa dimer containing two molecules of the bound coenzyme pyridoxal phosphate attached to lysine-258 (enclosed in box).85,86 (B) A stereoscopic view of a complete enzyme molecule which contains two identical subunits with the foregoing sequence. Coordinates from Arthur Arnone. In this “wire model” all the positions of all of the nearly 7000 atoms that are heavier than hydrogen are shown. The > 8000 hydrogen atoms have been omitted. The view is into the active site of the subunit on the right. The pyridoxal phosphate and the lysine residue to which it is attached are shown with heavy lines. The active site of the subunit to the left opens to the back side as viewed here. The drawing may be observed best with a magnifying viewer available from Abrams Instrument Corp., Lansing, Michigan or Luminos Photo Corp., Yonkers, New York. However, with a little practice, it is possible to obtain a stereoscopic view unaided. Hold the book with good illumination about 20–30 cm from your eyes. Allow your eyes to relax as if viewing a distant object. Of the four images that are visible, the two in the center can be fused to form the stereoscopic picture. Drawings by program MolScript (Kraulis, 1991).

Most of these have been deduced from the sequences of nucleotides in DNA. Sequences of some small peptide hormones and antibiotics. The molecular mass of a protein can be estimated from the chain length by assuming that each residue adds 100–115 Da.
The amino acid composition varies greatly among proteins. A typical globular protein contains all or most of the 20 amino acids. The majority are often present in roughly similar amounts but His, Cys, Met, Tyr, and Trp tend to be less abundant than the others. Specialized proteins sometimes have unusual amino acid compositions. For example, collagen of connective tissue contains 33 mole% glycine and 21% of proline + hydroxyproline residues; the major proteins of saliva contain 22% of glutamate + glutamine and 20–45% proline. Cell walls of plants contain both high proline and high glycine polypeptides. One from petunias is 67% glycine. Silk fibroin contains 45% glycine and 29% alanine. A DNA repair protein of yeast has 13 consecutive aspartate residues. The tough eggshell (chorion) of the domesticated silkmoth Bombyx mori contains proteins with ∼30% cysteine. Many proteins consist, in part, of repeated short sequences. For example, the malaria-causing Plasmodium falciparum in its sporozoite stage is coated with a protein that contains 37 repeats of the sequence NANP interspersed with 4 repeats of NDVP. These two sequences have been indicated with single-letter abbreviations for the amino acids.
With a large number of protein and DNA sequences available, it has become worthwhile to compare sequences of the same protein in different species or of different proteins within the same or different species. Computer programs make it possible to recognize similarities and homologies between sequences even when deletions and insertions have occurred. The term homology has the precise biological definition “having a common evolutionary origin,” but it is often used to describe any close similarity in sequence. Among a pair of homologous proteins, a change at a given point in a sequence may be either conservative, meaning that a residue of similar character (large, small, positively charged, nonpolar, etc.) has been substituted, or it may be nonconservative.