1. Fundamentals of Protein Structure

2. Our life is maintained by molecular network systems
Molecular network system in a cell
(From ExPASy Biochemical Pathways;

3. 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

4. Amino acid: Basic unit of protein
COO-
NH3+ C R H
Different side chains, R, determin the properties of 20 amino acids.
Amino group
Carboxylic acid group
An amino acid

5. White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic
20 Amino acids
Glycine (G)
Alanine (A)
Valine (V)
Isoleucine (I)
Leucine (L)
Proline (P)
Methionine (M)
Phenylalanine (F)
Tryptophan (W)
Asparagine (N)
Glutamine (Q)
Serine (S)
Threonine (T)
Tyrosine (Y)
Cysteine (C)
Asparatic acid (D)
Glutamic acid (E)
Lysine (K)
Arginine (R)
Histidine (H)
White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic

6. Proteins are linear polymers of amino acids
NH3＋ C
COOー ＋
NH3＋ C
COOー ＋ H H
A carboxylic acid condenses with an amino group with the release of a water
H2O
H2O R1 R2 R3
NH3＋ C CO NH C CO NH C CO H
Peptide bond H
Peptide bond H
The amino acid sequence is called as primary structure F T D A G S K A N G S

7. Amino acid sequence is encoded by DNA base sequence in a gene
DNA molecule
DNA base sequence ・ C G A T ＝

8. Amino acid sequence is encoded by DNA base sequence in a gene
Second letter T C A G
First letter
TTT
Phe
TCT
Ser
TAT
Tyr
TGT
Cys
Third letter
TTC
TCC
TAC
TGC
TTA
Leu
TCA
TAA
Stop
TGA
TTG
TCG
TAG
TGG
Trp
CTT
CCT
Pro
CAT
His
CGT
Arg
CTC
CCC
CAC
CGC
CTA
CCA
CAA
Gln
CGA
CTG
CCG
CAG
CGG
ATT
Ile
ACT
Thr
AAT
Asn
AGT
ATC
ACC
AAC
AGC
ATA
ACA
AAA
Lys
AGA
ATG
Met
ACG
AAG
AGG
GTT
Val
GCT
Ala
GAT
Asp
GGT
Gly
GTC
GCC
GAC
GGC
GTA
GCA
GAA
Glu
GGA
GTG
GCG
GAG
GGG

9. Gene is protein’s blueprint, genome is life’s blueprint
DNA
Genome
Gene
Gene
Protein
Protein

10. Gene is protein’s blueprint, genome is life’s blueprint
Glycolysis network
Genome
Gene
Protein

11. 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!

12. Each Protein has a unique structure
Amino acid sequence
NLKTEWPELVGKSVEEAKKVILQDKPEAQIIVLPVGTIVTMEYRIDRVRLFVDKLDNIAEVPRVG
Folding!

13. Basic structural units of proteins: Secondary structure
α-helix
β-sheet
Secondary structures, α-helix and β-sheet, have regular hydrogen-bonding patterns.

14. Three-dimensional structure of proteins
Tertiary structure
Quaternary structure

15. 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）

16. Close relationship between protein structure and its function
Example of enzyme reaction
Hormone receptor
Antibody
substrates A
enzyme
enzyme B
Matching the shape to A
Digestion of A!
enzyme A
Binding to A

17. Protein structure prediction has remained elusive over half a century
“Can we predict a protein structure from its amino acid sequence?”
Now, impossible!

18. 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.