TUTORIAL ON PEPTIDE AND PROTEIN STRUCTURE

I. PRIMARY STRUCTURE.

                                                Copyright: J. E. Wampler, 1996

This tutorial covers the basics of peptide and protein primary structure starting with some definitions followed by brief discussions of the amino acids, the formation of the peptide bond, the nomenclature of peptides and crosslinking in proteins.

FIRST SOME DEFINITIONS:

AMINO ACID
Proteins are polymers formed from alpha-amino carboxylic acids. The alpha- carbon is typically optically active and, in proteins, in the L-configuration.

Related Topic: Amino Acid Stereo Configuration


PEPTIDE
Two or more amino acids covalently linked by an amide bond between the carboxylic acid group of one and the alpha-amino group of the other.



POLYPEPTIDE
A long peptide chain (typically with MW<10,000).

PEPTIDE BOND
The amide, covalent linkage of peptides.

PROTEIN
A large macromolecule composed of one or more polypeptide chains.

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AMINO ACIDS:

18 of the 20 commonly occurring, genetically encoded amino acids involved in protein structure have a primary alpha-amino group and an optically active alpha-carbon center. All also have an alpha hydrogen atom. The names of the amino acids then specify the fourth substituent attached at this position.




1 is not optically active, but does have a primary amine







1 is optically active, but has a secondary amine





IN ADDITION there are other amino acids in proteins:

Naturally occuring chemical modifications of the 20 genetically encoded amino acids, eg.
Hydroxylation of proline and lysine

Phosphorylation of Serine & Tyrosine

R-group methylation of lysine, histidine and arginine.

R-group acetylation of lysine.

N-terminal methylation of alanine.

N-terminal acetylation of serine.

N-terminal formylation of methionine.

Addition of carbohydrates (at Asparagine and Serine).

Addition of Lipids (at Cysteine, N-terminal glycine and C-terminal via carbohydrate linker group)

Covalent attachment of cofactors (eg. pyridoxal-5-phosphate attached at lysine; hemes attached at cysteines).

More Information about the Amino Acids
Optical Activity and Stereo Configuration
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Formation of the peptide bond:

Thus the polymer formed is an unbranched chain of amino acids.

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Peptide Nomenclature:

Always referred to from N-terminal(amino) to the C-terminal (carboxy).

eg. Glycyl-alanyl-tyrosyl-glycine

Extended TRANS conformation (shown) where each torsion angle along chain is 180o

Short peptides are often given a general name according to how many residues (amino acids) are linked together.

Glycyl-alanyl-tyrosyl-glycine is a "TETRAPEPTIDE"

Alanyl-valyl-tryptophane is a "TRIPEPTIDE"

A general name for a long peptide is oligopeptide or POLYPEPTIDE.

CYCLIC PEPTIDES are formed when an amide (or peptide) bond is formed between the N-terminal and C-terminal residues.

CROSSLINKING IN PROTEINS.

The most common covalent crosslink between peptide chains is the disulfide bond formed by two cysteine residues.

In some connective tissue proteins crosslinks are formed by chemical modification. In collagen, lysine and histidine residues are used. In elastin the aromatic crosslinks, desmosine and isodesmosine, are formed from modified lysyl residues.

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Return to Introduction.
Continue to Part II.