Proteins

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Proteins

• ---From amino acids to polypeptides

Structural representation for two of the
polypeptides of deoxyhemoglobin
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Overview of lecture

• What are proteins
• Distance and time scales
• Basic amino acid structure
• L- vs. D-stereoisomers
• Classification, structure, and nomenclature of
  amino acids
• Amino acid modifications
• Peptide bond formation and structure
• Disulfide bond formation

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What are proteins

• Proteins are linear polymers (chains) of amino
  acids

Human insulin chain A
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Amino acid
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Asymmetric Carbon

• The asymmetric carbon of the AA
• All amino acid (except glycine) have chiral
  centers.
• Two kinds of AA, the L form and D form.
• All proteins in our body contain AA in L form.

Chiral carbon - A carbon atom with four different
substituents attached.
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Ionization of AA

• COOH
• NH2
• R group
• Isoelectric point (pI)

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Standard amino acid

• Twenty coding amino acid-DNA sequence
• New amino acids (2)
• No protein amino acids
• MW 110

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There are 20 L-amino acids in protein, each with
unique side chains
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Essential and Nonessential

• Of these 20 amino acids, 9 cannot be synthesized
  by our body.
• These 9 amino acids are therefore classified as
  essential AAs and must be included as part of our
  diet..
• Essential and nonessential Amino acids in Humans
• Essential
• Methionine Histidine Phenylalanine Isoleucin
  e
• Threonine Leucine Lysine
  Valine
• Arginine Tryptophan

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L -Glyceraldehyde
L - Alanine

Amino Acids

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GROUPS OF AMINO ACIDS
1. Aliphatic amino acids 2. Hydroxy amino
acids 3. Acidic amino acids 4. Amide amino
acids 5. Basic amino acids 6. Sulfur-containing
amino acids 7. Aromatic amino acids 8. Secondary
amino acids
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Aliphatic Amino Acids
Glycine (GLY)
Alanine (ALA)
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Aliphatic Amino Acids
Leucine (LEU)
Valine (VAL)


H
H


-
-
NH
C COO
NH
C COO
3
3
CH
2
CH
CH
CH
CH
3
CH
CH
3
3
3
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Aliphatic Amino Acids
Isoleucine (ILE)

H

-
NH
C COO
3
CH
CH
CH
CH
2
3
3
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Amino Acids with Alcohol
Serine (SER)
Threonine (THR)


H
H

-
NH
C COO

-
3
NH
C COO
3
CH
OH
OH
CH
2
CH
3
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Acidic Amino Acids
Aspartic Acid (ASP)
Glutamic Acid (GLU)


H
H

-
NH
C COO

-
3
NH
C COO
3
CH
2
CH
2
CH
2
-
COO
-
COO
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Amino Acids with Amides
Asparagine (ASN)
Glutamine (GLN)


H
H

-
NH
C COO

-
3
NH
C COO
3
CH
2
CH
2
CH
2
C NH
2
C NH
2
O
O
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Basic Amino Acids
Lysine (LYS)
Arginine (ARG)


H
H

-
NH
C COO
3

-
NH
C COO
3
CH
2
CH
2
CH
2
CH
2
CH
2
CH

CH
2
NH
2
2

NH
3
NH C NH
2
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Basic Amino Acids
Histidine (HIS)

H

-
NH
C COO
3
CH
2
NH
HN

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Sulfuric Amino Acids
Cysteine (CYS)
Cystine (CYS-CYS)

H


-
NH
C COO
-
-
COO
3
COO


NH
CH CH
S S CH
CH NH
CH
3
2
2
3
2
SH
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Sulfuric Amino Acids
Methionine (MET)

H

-
NH
C COO
3
CH
2
CH
2
S
CH
3
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Aromatic Amino Acids
Phenylalanine (PHE)
Tyrosine (TYR)
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Aromatic Amino Acids
Tryptophan (TRY)
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Secondary Amino Acids
Proline (PRO)
Hydroxyproline (HYP)
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Disulfide bonds stabilize protein structures
Ribonuclease catalyzes the hydrolysis of RNA
molecules.
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Disulfide bond formation is reversible
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The histidine side chain can serve as both a
proton donor and a proton acceptor
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Some amino acids are modified after the protein
is synthesized

• Modifications that occur after the protein is
  synthesized are called post-translational
  modifications

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Protein phosphorylation can increase or decrease
enzyme activity
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Linkage of a glycosaminoglycan to protein
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Amino acids are joined by peptide bonds
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Proteins are polypeptide chains

• The beginning of the protein is known as the
  amino-terminus and the end of the protein is
  known as the carboxyl-terminus.

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Peptide Bond

• Two amino acids linking - Dipeptide
• 3 amino acids - Tripeptide
• 5 - 30 amino acids - Polypeptide
• 30 - 50 - Proteins

Ala-Val
Ala-Val-Gly
Ala-Val-Gly-Tyr-Trp-Met-Glu-Lys
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The peptide bond has partial double bond character
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Peptide bonds can be either cis or trans
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Interconversion of cis and trans prolines
requires breaking and reforming a covalent bond

• cis-trans isomerization of Pro is slow in the
  absence of an enzyme (prolyl isomerase).

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Angles of the chain

• Due to the partial double bond character of the
  peptide bond, free rotation only occurs around
  the f and y angles

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Angles of the chain
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The conformational angles

• Peptides are rigid
• There is rotational freedom at each Ca bond
• The N-Ca angle is called phi (f)
• The Ca-C angle is called psi (y)
• The AA sequence and the phi-psi angles completely
  specify a three dimensional structure

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Constraints on conformation

• Most phi-psi combinations cant occur because
  they cause the side chain and main chain to
  collide
• Permitted combinations are called Ramachandran
  plots

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Glycines structural role

• Glycine (H side chain) has lots of freedom
• Good for creating unusual shapes
• Glycine is highly conserved among homologous
  sequences

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Summary

• Proteins are made up of chains of AAs
• L- vs. D-stereoisomers
• Classification of AAs into hydrophobic, acidic,
  basic, polar, and aromatic
• Know the amino acid side chains!
• Amino acids are joined by peptide bonds
• Peptide bond has partial double bond character,
  giving the peptide bond a rigid character