Introduction to Proteins

Protein Basics

• The basic categories include Proteins, Carbohydrates, Lipids, and DNA/RNA
• Focus is given to what they are and what their structure is, including chemical and physical make-up, bonds and folding

Proteins

• Perform many functions in the body
• These functions range from structure and support to catalysis of reactions, transport, defense, development and regulation, and movement
• Examples of proteins includes collagen, elastin, enzymes, hemoglobin, antibodies, cytokines, hormones, and myosin
• Enzymes and antibodies have industrial applications and medical uses as drugs

Protein Structure

• Proteins are polymers of amino acids
• There are 20 different amino acids commonly found in proteins
• Proteins are formed by joining amino acids together in a long linear chain
• What makes each protein unique is the order and number of the amino acids in the polypeptide chain
• The number of possibilities = 25,600,000,000

Amino Acids

• Amino acids have a common structure and are building blocks for proteins
• The central carbon (α-carbon) is bonded to an amino group (NH2), a carboxyl group (COOH), hydrogen, and a side chain or R-group
• The R-group is what varies among the 20 different amino acids

Stereoisomers

• Amino acids are stereoisomers
• The central α-carbon is chiral, forming an asymmetric molecule
• Amino acids can have 2 different stereoisomers: L and D forms
• All amino acids (except Glycine) exist in D and L forms
• Only L-forms are found in proteins

Amino Acids and Charge

• In water, amino acids are ionized and exist as dipolar ions (zwitterions)
• In this situation, NH2 becomes NH3+ and COOH becomes COO-
• R-groups can also contribute charge and some are highly charged
• Overall charge on the protein is determined by the sequence of amino acids
• Overall charge affects the shape of a protein

R-Groups in Amino Acids

• 20 different R-groups give rise to the 20 different amino acids
• R-groups are divided into nonpolar (uncharged and hydrophobic), polar (uncharged and hydrophilic), and charged at cellular pH
• 9/10 are nonpolar ex. Alanine
• 5/6 are polar ex. Cysteine
• 5 are charged ex. Lysine
• Proline is the only amino acid that is cyclic
• Cysteine and Methionine contain sulphur

Protein Code

• Each amino acid has a three letter code and one letter code abbreviation

Peptide Bonds

• Amino acids are joined together to form chains through peptide bonds
• A peptide bond occurs between the carboxyl group of one amino acid and the amino group of another
• Dehydration (condensation) reactions result in the removal of H2O
• Resulting bond is covalent (C-N), peptide bond, and quite rigid
• Additional amino acids can be added at the carboxyl end

Peptides

• Peptide is a short sequence (chain) of amino acids, generally less than 50 amino acids
• A chain of 2 amino acids is a di-peptide, 3 is a tri-peptide, etc
• The start of a peptide chain is the N-terminus (amino group) and the end is the C-terminus (carboxyl group)
• The backbone sequence is N-C-C (nitrogen, carbon, carbon) with R-groups attached to carbon

Polypeptides

• Polypeptides have a larger number of amino acids joined to form chains
• The number of amino acids varies between 50 to over 1000
• Some proteins consist of several polypeptide chains linked together
• The unit of size for proteins is called Dalton (Da)
• 1 Da = one atomic mass unit
• The molecular weight of amino acids varies from 75 Da for Glycine to 186 Da for Tryptophan; average = ~120 Da
• The molecular weight of proteins can vary from 1,000 to >100,000 Daltons (1kDa to >100kDa)

Peptide Drugs

• The market for peptide drugs is >$45 billion
• There are currently >100 peptide drugs on the market with more in clinical trials
• Oxytocin has 9 amino acids and is used for inducing labor (produced synthetically)
• Many peptide drugs are isolated from natural sources or by semi-synthetic modification of natural material

Summary of Protein Info

• Proteins are polymers composed of amino acids
• The basic structure of an amino acid contains an amino group, a carboxylic acid group (common), and an R-group (unique)
• Amino acids contain both positive and negative charge
• There are 20 standard amino acids with 20 R-groups that vary in size and charge
• Depending on the R group, amino acids can be hydrophobic or hydrophilic
• Amino acids are joined together via peptide bonds
• Amino acids form peptide chains which begin at the N-terminus and end at the C-terminus
• The shape and charge (and therefore function) of a protein is related to the composition and order of amino acids