AMINO ACIDS

predominant form at pH 1 (below the pK a of both ionizable groups)

+ NH 3

predominant form at pH 7 (dipolar ion, i.e. "zwitterion")

+ NH 3

predominant form at pH 11 (above the pKa of both ionizable groups) :NH2 H C R COO

pKa ~2 COOH H+ H

pKa ~9.5 COO H+

C R

C R

L-isomer H3N+

COO C R H

OOC

D-isomer
+ NH 3

C R

"R" groups (amino acid side chains) provide proteins with their unique structural and functional properties. There are 20 different L-amino acids (with 20 different R groups) commonly found in proteins. Individual proteins differ in amino acid composition.

ALIPHATIC SIDE CHAINS (nonpolar)

Longer hydrocarbon chains are more hydrophobic. Glycine (Gly) COO
+H N 3

Alanine (Ala) COO

+H N 3

Valine (Val) COO

Leucine (Leu) COO

+H N 3

Isoleucine (Ile) COO

+H N 3

C H H

C H CH3

+H N 3

C H

C H CH2

C H CH CH3 CH2 CH3

CH H3C CH3

Proline (Pro) COO

+H N 2

CH H3C CH3

C H CH2 CH2

H2C

p. 1

COO
+H N 3

R AROMATIC SIDE CHAINS

Phenylalanine (Phe) CH2 Tyrosine (Tyr) CH2 Tryptophan (Trp) CH2

NH

OH

HYDROXYL-containing
Serine (Ser) CH2 OH also Tyrosine (aromatic) Threonine (Thr) CHOH CH3

SULFUR-containing
Cysteine (Cys) CH2 SH Methionine (Met) CH2 CH2 S CH3

ACIDIC
Aspartate (Asp) CH2 COO Glutamate (Glu) CH2 CH2 COO O

AMIDES
Asparagine (Asn) Glutamine (Gln) CH2 CNH2 O CH2 CH2 CNH2

p. 2

BASIC SIDE CHAINS

Lysine (Lys) COO
+H N 3

Arginine (Arg) COO

+H N 3

Histidine (His) COO

+H N 3

C H CH2 CH2 CH2 CH2

+ NH 3

C H CH2 CH2 CH2 NH C NH2

C H CH2

HN

+H N 2

R GROUP IONIZATION REACTIONS: Group (moiety) Acid carboxyl (C-terminus, or R group of Glu or Asp) (carboxylic acid)

Base (carboxylate anion)

H+

RCOOH
amino (N-terminal -amino or -amino group of Lys) , (ammonium cation)

RCOO

H+

(amine)

RNH 3
thiol of Cys (sulfhydryl)

RNH 2
(thiolate anion)

H+

(thiol or sulfhydryl)

RSH
guanidino group of Arg (guanidinium cation)

RS

+
(guanidino)

H+

R NH
+H

R NH HN C NH 2 + H+

C
2N

NH 2

imidazole group of His

(imidazolium cation)

(imidazole)

R
HN

R
+ HN N H+

+NH

aromatic OH group of Tyr

(phenolic hydroxyl)

(phenolate anion)

R
+ H+

OH
p. 3

The 20 Standard Amino Acid Residues of Peptides and Proteins

Amino acid ( or residue) 3-letter symbol 1-letter symbol Mnemonic help for 1-letter symbol Approximate pK value of residue side chain in peptides & proteins

Alanine Ala A Alanine Glutamate Glu* E gluEtamic acid ~4.0 Glutamine Gln* Q Q-tamine Aspartate Asp** D aspar Dic acid ~4.0 Asparagine Asn** N asparagi N e Leucine Leu L Leucine Glycine Gly G Glycine Lysine Lys K (before L) ~10.0 Serine Ser S Serine Valine Val V Valine Arginine Arg R a Rginine ~12.0 Threonine Thr T Threonine Proline Pro P Proline Isoleucine Ile I Isoleucine Methionine Met M Methionine Phenylalanine Phe F F enylalanine Tyrosine Tyr Y t Y rosine ~10.0 Cysteine Cys C Cysteine ~8.5 Tryptophan Trp W t W o rings (or tW yptophan) Histidine His H Histidine ~6.5 ___________________________________________________________________ * Glx = either acid or amide (when it isn't known which it is) **Asx = either acid or amide (when it isn't known which it is)

NOTE:

While the -carboxyl groups of free amino acids have pK values close to ~2.0, the (terminal) -COOH group pKs of peptides and proteins are closer to neutrality, ~3.0 . While the -amino groups of free amino acids have pK values close to ~9.5, the (terminal) -amino group pKs of peptides and proteins are closer to neutrality, ~8.0 . ___________________________________________________________________

CLASSIFICATION OF AMINO ACID SIDE CHAINS) Nonpolar but rather H 2 O-soluble: (not hydrophobic) Gly Pro Polar, uncharged: Hydroxyl-containing: aliphatic OH aromatic OH Ser Tyr Thr Amide-containing: Asn Gln Sulfur-containing: Cys (thiol) Met (thioether) Nonpolar, hydrophobic: Ala Met Val Phe Leu (Trp) Ile (Cys) Charged (at pH 6-7), polar: Acidic () Basic (+) Asp (carboxyl) Lys (-amino) Glu (carboxyl) Arg (guanidino) (His) (imidazole) Ionizable but predominantly uncharged at pH 6-7: Cys (thiol) Tyr (phenolic OH) Aromatic: Phe Tyr Trp p. 4