The amino acids, peptide bonds, and the primary structure of

proteins

Chem 333 week #1

9/10/01 - 9/14/01

Protein structure is often discussed in terms of a hierarchy

Amino acids are the building blocks of proteins

• Three major parts: carboxyl group, amino group, and side chain.

• Central C atom called alpha carbon.

• Amino acids can differ in their side chains (R).

• The alpha carbon is a chiral center.

Two enatiomers possible for most amino acids

L-form found almost exclusively in naturally occurring proteins

The nonpolar amino acids

The charged amino acids

The polar amino acids

Glycine is pretty unique

• Smallest side chain

• No chiral center

• Neither very polar or nonpolar

Polarity can be hard to quantify

Review: acid-base chemistry

• Acid : Proton (hydrogen ion, H+) donor• Base: Proton (hydrogen ion, H+) acceptor

H Cl O

H

H Cl- O

H

HH+ +

+

Acid

Base Hydronium ion

The reaction when an acid is dissolved in water can written as an equilibrium:

HA (aq) + H2O (l) H3O+ (aq) + A- (aq)

acid base conjugate acid

conjugate base

The acid-base equilibrium is characterized by a constant Ka

HA (aq) + H2O (l) H3O+ (aq) + A- (aq)

Ka =[H3O

+][A−][HA]

=[H+][A−]

[HA]

HA (aq) H+ (aq) + A- (aq)

pKa = -log Ka

Some pKa facts

• The lower the pKa, the stronger the acid (smaller pKa--> larger Ka --> larger [H+])

• Acetic acid has pKa 4.8

– Ka = 10^-4.8 = 1.5 x 10-5

Henderson-Hasselbach equation relates pKa, pH, and [A-]/[HA]

pH=pKa +logA−

[ ]HA[ ]

⎛

⎝ ⎜ ⎜

⎞

⎠ ⎟ ⎟

Applications of the Henderson-Hasselbach Equation

• When pH = pKa, [A-] = [HA]

– Concentrations of protonated and unprotonated forms are equal

• If you know the pH and pKa, you can determine whether an amino acid is charged or uncharged

pKa’s can vary depending on environment

• Effect of solvent environment.

• Effect of specific local interactions.

Amino acids join together by forming peptide bonds

Proteins are chains of these peptide units (polypeptides)

Two backbone torsion angles : phi (and psi ()

Possible and angles are given in a Ramachandran plot

Cysteines can form disulfide bonds

Proteins are synthesized in vivo based on information encoded in genes

DNA--->RNA-->Protein

RNA is synthesized from a DNA template

Chromosomal DNA

Nascent RNA molecules

Protein synthesis occurs at ribosomes

The Genetic code

After translation, some proteins undergo further covalent modification

• Proteolytic processing• Phosphorylation: addition of a phosphate group

(PO43-) to a Ser or Tyr residue.

• Glycosylation: addition of sugar groups to Asn (N-glycosylation) or Ser (O-glycosylation).

• Alteration of chain termini– Removal of N-Met

– Acetylation and amidation

Preproinsulin is cleaved after translation to give insulin

Phosphorylation can modulate protein function

Proteins can be glycosylated at either Asn (N-linked) or Ser/Thr (O-linked)