Protein English

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Fundamentals of Protein Structure
August, 2006 
Tokyo University of Science Tadashi Ando
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Our life is maintained by molecular network systems 
Molecular network system in a cell
(From ExPASy Biochemical Pathways; http://www.expasy.org/cgi-bin/show_thumbnails.pl?2)
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Proteins play key roles in a living system
Three examples of protein functions
Catalysis: Almost all chemical reactions in a living cell are catalyzed by protein enzymes.
Transport: Some proteins transports various substances, such as oxygen, ions, and so on.
Information transfer: For example, hormones.
Alcohol dehydrogenase oxidizes alcohols to aldehydes or ketones
Haemoglobin carries oxygen
Insulin controls the amount of sugar in the blood
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Amino acid: Basic unit of protein
An amino acid
Different side chains, R, determin the properties of 20 amino acids.
Amino group
Carboxylic acid group
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20 Amino acids
Glycine (G)
Glutamic acid (E)
Asparatic acid (D)
Methionine (M)
Threonine (T)
Serine (S)
Glutamine (Q)
Asparagine (N)
Tryptophan (W)
Phenylalanine (F)
Cysteine (C)
Proline (P)
Leucine (L)
Isoleucine (I)
Valine (V)
Alanine (A)
Histidine (H)
Lysine (K)
Tyrosine (Y)
Arginine (R)
White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic
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Proteins are linear polymers of amino acids
R1
NH3＋
C
CO
H
R2
NH
C
CO
H
R3
NH
C
CO
H
R2
NH3＋
C
COOー
H
＋
R1
NH3＋
C
COOー
H
＋
H2O
H2O
Peptide bond
Peptide bond
The amino acid sequence is called as primary structure 
A
A
F
N
G
G
S
T
S
D
K
A carboxylic acid condenses with an amino group with the release of a water
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Amino acid sequence is encoded by DNA base sequence in a gene
DNA molecule
＝
DNA base sequence
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Amino acid sequence is encoded by DNA base sequence in a gene
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Gene is protein’s blueprint, genome is life’s blueprint 
Gene
Genome
DNA
Protein
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Gene is protein’s blueprint, genome is life’s blueprint 
Genome
Glycolysis network
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In 2003, Human genome sequence was deciphered!
Genome is the complete set of genes of a living thing.
In 2003, the human genome sequencing was completed.
The human genome contains about 3 billion base pairs.
The number of genes is estimated to be between 20,000 to 25,000.
The difference between the genome of human and that of chimpanzee is only 1.23%!
3 billion base pair => 6 G letters 
& 
1 letter => 1 byte
The whole genome can be recorded in just 10 CD-ROMs!
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Each Protein has a unique structure
Amino acid sequence
NLKTEWPELVGKSVEEAKKVILQDKPEAQIIVLPVGTIVTMEYRIDRVRLFVDKLDNIAEVPRVG
Folding!
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Basic structural units of proteins: Secondary structure
α-helix
β-sheet
Secondary structures, α-helix and β-sheet, have regular hydrogen-bonding patterns.
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Three-dimensional structure of proteins
Tertiary structure
Quaternary structure
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Hierarchical nature of protein structure
Primary structure (Amino acid sequence)
↓
Secondary structure （α-helix, β-sheet）
↓
Tertiary structure （Three-dimensional structure formed by assembly of secondary structures）
↓
Quaternary structure （Structure formed by more than one polypeptide chains）
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Close relationship between protein structure and its function
enzyme
A
B
A
Binding to A
Digestion of A!
enzyme
Matching the shape to A
Hormone receptor 
Antibody
Example of enzyme reaction
enzyme
substrates
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Protein structure prediction has remained elusive over half a century
“Can we predict a protein structure from its amino acid sequence?”
Now, impossible!
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Summary
Proteins are key players in our living systems.
Proteins are polymers consisting of 20 kinds of amino acids.
Each protein folds into a unique three-dimensional structure defined by its amino acid sequence.
Protein structure has a hierarchical nature.
Protein structure is closely related to its function.
Protein structure prediction is a grand challenge of computational biology.