lecture 3

Proteins

• Major agents of biological function

  • present in all cells

  • vary enormously in size

  • have extensive functional diversity

• Gene expression

  • molecular instruments through which genetic information is expressed

  • more diverse than the set of genes that encode them

• Amino acid composition

  • formed mainly from 20 common amino acids

  • other amino acids are occasionally found in proteins

• Structure

  • amino acids are covalently linked in a linear sequence

  • amino acid side chains give proteins distinct chemical properties

Amino acid basics

• Most amino acids are chiral

  • allows stereospecific interactions

• R group

  • gives each amino acid its distinct chemical properties

• Nonstandard amino acids

  • also exist

  • can have important biological roles

Amino acids as building blocks of proteins

• Proteins are linear heteropolymers of α-amino acids

• Amino acids are joined by condensation reactions

• Amino acids are well suited for many biological functions because they have:

  • capacity to polymerize

  • useful acid-base properties

  • varied physical properties

  • varied chemical functionality

Shared features of amino acids

• Amino acids differ mainly in their R group

• α-carbon

  • tetrahedral

  • bonded to 4 substituents

• Most amino acids have:

  • acidic carboxyl group

  • basic amino group

  • α-hydrogen

  • unique R group

• Exceptions

  • proline has a modified amino group because its side chain bonds back to the nitrogen

  • glycine’s R group is H

    • gives the α-carbon 2 hydrogens

    • therefore glycine is not chiral

D vs L amino acids

• D and L designations are based on the configuration of glyceraldehyde

• For amino acids, D and L refer to configuration around the chiral center

• They do not indicate the direction the molecule rotates plane-polarized light

Amino acid atom naming

• Biochemical naming starts at the α-carbon and moves outward along the R group

• Side-chain carbons are named in order:

  • α

  • β

  • γ

  • δ

  • ε

General properties of amino acids

• Each free amino acid has at least 2 pKₐ values

  • one for the α-carboxyl group

  • one for the α-amino group

• Some side chains also contain ionizable groups

  • gives those amino acids additional pKₐ values

• At physiological pH, free amino acids are zwitterionic

  • amino group is protonated

  • carboxyl group is deprotonated

  • allows amino acids to act as both acids and bases

• Solubility

  • most are highly soluble in water

  • minimally soluble in organic solvents

  • due to their ionic nature

Nonpolar amino acids

• Glycine

• Alanine

• Proline

• Valine

• Leucine

• Isoleucine

• Methionine

• General properties

  • stabilize protein structure through hydrophobic interactions

  • often located in the protein interior

  • often among the most conserved amino acids in protein sequences

• Structural differences

  • proline has a rigid structure

  • glycine has a very flexible structure

  • glycine and proline are especially often conserved

Aromatic amino acids

• Phenylalanine

• Tyrosine

• Tryptophan

• General properties

  • participate in hydrophobic interactions

  • absorb UV light around 280 nm

• Tyrosine

  • has a hydroxyl group

  • can participate in hydrogen bonding

• Tryptophan

  • has fluorescent properties

Polar uncharged amino acids

• Serine

• Threonine

• Cysteine

• Asparagine

• Glutamine

• General properties

  • often found on protein surfaces

  • interact with water through hydrogen bonding

• Cysteine

  • readily forms disulfide bonds

  • two cysteines linked by a disulfide bond form cystine

Positively charged amino acids

• Lysine

• Arginine

• Histidine

• General properties

  • carry significant positive charge at neutral pH

  • often act as proton donors or acceptors

• Histidine

  • side-chain pKₐ ≈ 6

  • can readily gain or lose a proton near biological pH

Negatively charged amino acids

• Aspartic acid (aspartate)

• Glutamic acid (glutamate)

• General properties

  • structurally similar to asparagine (Asn) and glutamine (Gln)

  • carry significant negative charge at neutral pH

  • can act as proton donors or acceptors

Modified amino acids found in proteins

• Usually not incorporated directly by ribosomes

  • exception: selenocysteine

• Typically arise through post-translational modification of proteins

• Reversible modifications

  • especially phosphorylation

  • important in regulation and signaling

Amino acids as acids and bases

• Amino acids commonly exist in zwitterionic form

• Have characteristic titration curves

• Isoelectric point, pI

  • pH at which the amino acid has no net charge

• pKₐ values of functional groups

  • can change depending on the local environment

• Some amino acids

  • carry a net charge at neutral pH

Isoelectric point

• Isoelectric point, pI

  • pH at which a molecule has no net charge

• Amino acids without ionizable side chains, such as glycine

  • only consider the α-amino and α-carboxyl groups

• Amino acids with ionizable side chains

  • first identify the species with net charge = 0

  • then use the two pKₐ values that surround that neutral species

Formation of peptides

• Peptides

  • small condensation products of amino acids

• Peptide bond

  • covalent

  • formed by condensation

  • broken by hydrolysis

• Numbering and naming

  • start at the amino terminus