Chapter 3: The Amino Acids:

1
Chapter 3The Amino Acids
Protein structure is key to function Amino Acid
structure is key to shape
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Basic Structure

• CHIRAL ?-CARBON SUBSTITUTIONS
• Carboxyl
• Primary Amines
• Single Hydrogen
• R Group (20 standard a.a.s)

COO -
NH3
?
C
H
R
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L- versus D- Convention

• Fischer convention Horizontal lines project
  toward the readers vertical lines project away.

CHO
CHO
HO
OH
H
H
CH2OH
CH2OH
L-Glyceraldehyde
D-Glyceraldehyde
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Lysine (Lys, K)
COO -
NH3
C
H
?
CH2CH2CH2CH2NH2 ? ? ? ?
5
L- versus D- Convention

• Fischer convention Horizontal lines project
  toward the readers vertical lines project away.

CHO
CHO
HO
OH
H
H
CH2OH
CH2OH
L-Glyceraldehyde
D-Glyceraldehyde
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Carbohydrates

• Fischer convention Horizontal lines project
  toward the readers vertical lines project away.

CHO
CHO
H
HO
OH
H
CH2OH
CH2OH
L-Glyceraldehyde
D-Glyceraldehyde
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Basic Structure

• CHIRAL ?-CARBON SUBSTITUTIONS
• Carboxyl
• Primary Amines
• Single Hydrogen
• R Group (20 standard a.a.s)
• L-ENANTIOMERS
• Naturally occurring
• Rotation right or left
• All but one is S

COO -
NH3
?
C
H
R
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R versus S
NH3
- OOC
?
C
H
CH2R
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Cysteine (Cys, C)
NH3
- OOC
?
C
H
CH2SH
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Amino Acid General Properties
COO -

• Zwitterions two ionizable groups with opposite
  charges
• pK1 2.2 (1.7 2.6)
• pK2 9.4 (8.9 10.8)
• pK3 - ?

NH3
?
C
H
R
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Amino Acid Classification
NONPOLAR Ala (A) Val (V) Leu (L) Ile (I) Pro
(P) Phe (F) Trp (W) Met (M) Gly (G)
POLAR, UNCHARGED Gly (G) Ser (S) Thr (T) Cys
(C) Gln (Q) Tyr (Y) Asn (N)
CHARGE Lys (K) (10.54) Arg (R) (8.99) His (H)
(6.04)
R
- CHARGE Asp (D) (3.90) Glu (E) (4.07)
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Amino Acid Classification
NONPOLAR Ala (A), Val (V), Leu (L), Ile (I) -
aliphatic Pro (P) cyclic pyrrolidine Phe (F),
Trp (W) - aromatic Met (M) thiol ether
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Amino Acid Classification
POLAR, UNCHARGED Ser (S), Thr (T) -
hydroxylic Cys (C) disulfide-forming thiol Asn
(N), Gln (Q) - amides Tyr (Y) phenolic
(hydroxyl benzene) Gly (G) simple H
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Amino Acid Classification
CHARGE Lys (K) butyl/?-amine (pK
10.58) Arg (R) - ?-guanidino (pK 12.48) His (H)
- imidazolium (pK 6.04) - CHARGE Asp (D) -
?-carboxyl (pK 3.86) Glu (E) - ?-carboxyl (pK
4.25)
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Acid Base Properties
H2N CH2 COO -
pK2 9.78
pI 6.07
Isoelectric Point pI ½ (pK1 pK2)
H3N CH2 COO -
pK1 2.35
H3N CH2 COOH
What are the pIs for K, R, D, E, and H?
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Lysine (Lys, K)
COO -
NH3
C
H
?
CH2CH2CH2CH2NH3 ? ? ? ?
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Notes on pKas

• pKa1 of Glycine lt monocarboxylic acid (Acetic
  Acid, pKa 4.76 Gly, pKa 2.34)
• NH3 of Glycine gt ammonia, pKa 9 Gly, pKa
  9.6, e.g., Lysine)
• Electronic influence of local (intra- and
  inter-molecular) functional groups affect the
  molecule

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Notes on Nomenclature

• Glx and Asx for Glu/Gln and Asp/Asn
• Small peptides
• AYDG Alanyltyrosylaspartylglycine
• Glutathione ?-L-glutamyl L-cysteinylglycine
  
• Peptides are always written N to C
• Primary chain named in sequence of the Greek
  alphabet from the peptide carbonyl
• (alpha, beta, gamma, delta, epsilon)

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Nonstandard Amino Acids

• Post-translational modifications (where?)
  hydroxylation, methylation, acetylation,
  carboxylation and phosphorelation e.g., HOPro,
  HOLys, PhosphoSer, MethylHis
• D-amino acids in some bacteria and in
  enzymatically produced peptides
• Lipoproteins (lipid), Glycoproteins
  (carbohydrate) connect via reactive R-groups
• Selinocysteine

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Bioactive Amino Acids

• Serotonin Tryptophan hydroxylation/
  decarboxylation (lows)
• Epinephrine (adrenaline) Tyrosine
  decarboxylation (highs)
• MAO inhibitors
• Histamine Histidine decarboxylation
• GABA Glutamine decarboxylation

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Bioactive Peptides

• Aspartylphenylalanine methylester Nutrasweet
• Glutathione ?-glutamylcysteinylglycine
• Enkephalins natural opiates/analgesics
• Y-G-G-F-L Y-G-G-F-M
• Vaospressin Oxytocin

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Peptide Bond Formation
O
R
NH3
C
CH
O-
NH3
CH
C
O-
O
R
H2O Condensation
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Tripeptide Structure
C-terminus
N-terminus
O
R
H
COO-
C
N
CH
NH3
CH
N
CH
C
O
H
R
R
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Canonical Peptide Bond Structures
-
O
O
C
C
or
N
N

H
H
Resonance or Tautomerism restricts peptide
bond rotation
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trans configurationabout the peptide bond
linkage
R
O
H
COOH
C
N
CH
NH2
CH
N
CH
C
O
H
R
R
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Primary Protein Structure
O
R
H
COO-
C
N
CH
NH3
CH
N
CH
C
O
H
R
R
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Generic Formula
R
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PROTEIN SYNTHESIS
DNA
Transcription
mRNA
Translation
Globular Protein
Amino Acids
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COO -
NH3
C
H
?
CH3
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Alanine (Ala, A)
COO -
NH3
C
H
?
CH3
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COO -
NH3
C
H
?
CH2CH2SCH3
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Methionine (Met, M)
COO -
NH3
C
H
?
CH2CH2SCH3
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COO -
NH3
C
H
?
CH2CONH2
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Asparagine (Asp, N)
COO -
NH3
C
H
?
CH2CONH2
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COO -
NH3
C
H
?
CH(OH)CH3
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Threonine (Thr, T)
COO -
NH3
C
H
?
CH(OH)CH3
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COO -
NH3
C
H
?
CH2CH2COO-
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Glutamate (Glu, E)
COO -
NH3
C
H
?
CH2CH2COO-
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COO -
NH3
C
H
?
CH2 OH
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Tyrosine (Tyr, Y)
COO -
NH3
C
H
?
CH2 OH
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COO -
NH3
C
H
?
NH
CH2
N H
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Histidine
COO -
NH3
C
H
?
NH
CH2
N H
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Histidine
Hückels Rule 4n 2 aromatic
COO -
NH3
C
H
?
NH
CH2
N H
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COO -
NH3
C
H
?
CH2
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Phenylalanine (Phe, F)
COO -
NH3
C
H
?
CH2
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COO -
CH2
CH2
?
C
CH2
H
NH2
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Proline (Pro, P)
COO -
CH2
CH2
?
C
CH2
H
NH2
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COO -
NH3
C
H
?
CH2CH2CH2CH2NH2 ? ? ? ?
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COO -
NH3
C
H
?
CH2SH
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Cysteine (Cys, C)
COO -
NH3
C
H
?
CH2SH
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Cysteine
NH3
- OOC
?
C
H
CH2SH
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Genomics vs Proteomics