Amino Acids, Peptides, Protein Primary Structure

Chapter 3

Amino Acids

• Basic struct’l units of prot’s• 3 common funct’l grps:

– -NH2, -COOH, -H

• Indiv aa’s each have diff R grp• 4 grps att’d to a C

– Is this a chiral C?

• At neutral pH: dipole (zwitterion)– Amino grp as NH3+

– Carboxyl grp as COO-

• Chiral C, so D,L stereo-isomers– L aa’s

polymerize prot’s

• Side chains vary: size, shape, charge, reactivity, H-bond capacity

• Five aa groups, based on R grp similarities

• Some notes:– Glycine – only optically inactive aa– Cysteine – highly reactive sulfhydryl grp– Histidine – R grp may be proton donor

or acceptor at physio pH

• 1) Nonpolar w/ aliphatic R grps– Glycine (Gly, G)– Alanine (Ala, A) – Proline (Pro, P)– Valine (Val, V)– Leucine (Leu, L)– Isoleucine (Ile, I)– Methionine (Met, M)

• 2) Aromatic R grps– Phenylalanin

e (Phe, F)– Tyrosine (Tyr,

Y)– Tryptophan

(Trp, W)– Hydrophobic

• 3) Polar w/ uncharged R grps– Serine (Ser, S)– Threonine (Thr, T)– Cysteine (Cys, C)– Asparagine (Asn, N)– Glutamine (Gln, Q)

• 4) Polar w/ + charged R grps at physio pH– Lysine (Lys, K)– Histidine (His, H)– Arginine (Arg, R)

• 5) Polar w/ - charged R grps at physio pH– Aspartate (Asp, D)– Glutamate (Glu, E)

Cysteine/Cystine

• Cys reactive SH grp oxidizes disulfide bond

• Forms cystine– Hydrophobic– Impt to protein

3D structure

Amino Acid Titration Curves

• Aa’s – weak acids– Titration curves for each– REMEMBER: Meas pH as titrate w/

OH-. Plot OH- added on x axis vs. pH on y axis

• 2 abstractable H’s, both on grps att’d to C (bottom p. 81)– Carboxyl grp– Amino grp

• 2 inflection pts– Shape of each sim to inflection seen

w/ monoprotic acid (Chpt 2)– Each aa has at least 2 pKa’s

• At titration midpoint([OH-]=1 eq), cmpd fully dipolar– No net electrical charge– “Isoelectric point”– Isoelectric pH = pI

• Each aa has characteristic pI– At any pH<pI, aa has net + charge– At any pH>pI, aa has net - charge

• pKa1 <<<< pKa2– First H+ released: much more easily

given up than second H+

• 2 pKa’s = 2 regions of buffering capacity

• Aa’s w/ ionizable R grps (lys, arg, his) have 3rd pKa

Peptide Bonds

• Link two aa’s Dipeptide– Condensation rxn

• What mol is removed??

– Endothermic – Stable under physio cond’s

• Broken w/ boiling in strong acid/base

carboxyl of aa1 joined to amino of aa2• In cells, bond form’n assisted by

ribosomes during translation

• Oligopeptide = several aa’s joined by peptide bonds

• Polypeptide = many aa’s = small protein– Protein commonly MW > 10,000

• Amino terminus = aa residue w/ free amino grp

• Carboxy terminus = aa residue w/ free carboxyl grp

• At neutral pH, all peptides have 1 free NH3+ and 1 free COO-

• BUT R grps on indiv aa may be ionized Characteristic pI

for each peptide

• Peptide ionization = sum of all R grp charges of aa’s in peptide