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

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- + H
O
H
H
Acid
Base
Hydronium ion
The reaction when an acid is dissolved in
water can written as an equilibrium:
HA (aq) + H 2 O (l)
acid
base
H3 O+ (aq) + A - (aq)
conjugate
acid
conjugate
base
The acid-base equilibrium is
characterized by a constant Ka
HA (aq) + H 2 O (l)
HA (aq)
H3 O+ (aq) + A - (aq)
H+ (aq) + A - (aq)
[H3O ][A ] [H  ][A  ]
Ka 

[HA]
[HA]
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]
A  


pH  pKa  log

HA
Applications of the HendersonHasselbach 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 (f)and psi (y)
Possible f and y 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 (Nglycosylation) 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)