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Fundamentals of Protein Structure August, 2006 Tokyo University of Science Tadashi Ando.

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Presentation on theme: "Fundamentals of Protein Structure August, 2006 Tokyo University of Science Tadashi Ando."— Presentation transcript:

1 Fundamentals of Protein Structure August, 2006 Tokyo University of Science Tadashi Ando

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 - NH 3 + C R H An amino acid Different side chains, R, determin the properties of 20 amino acids. Amino groupCarboxylic acid group

5 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

6 Proteins are linear polymers of amino acids R1R1 NH 3 + C CO H R2R2 NH C CO H R3R3 NH CCO H R2R2 NH 3 + C COO ー H + R1R1 NH 3 + C COO ー H + H2OH2O H2OH2O Peptide bond The amino acid sequence is called as primary structure AA F N G G S T S D K A carboxylic acid condenses with an amino group with the release of a water

7 Amino acid sequence is encoded by DNA base sequence in a gene ・CGCGAATTCGCG・・CGCGAATTCGCG・ ・GCGCTTAAGCGC・・GCGCTTAAGCGC・ DNA molecule = DNA base sequence

8 Amino acid sequence is encoded by DNA base sequence in a gene Second letter TCAG First letter T TTT Phe TCT Ser TAT Tyr TGT Cys T Third letter TTCTCCTACTGCC TTA Leu TCATAA Stop TGA Stop A TTGTCGTAGTGG Trp G C CTT Leu CCT Pro CAT His CGT Arg T CTCCCCCACCGCC CTACCACAA Gln CGAA CTGCCGCAGCGGG A ATT Ile ACT Thr AAT Asn AGT Ser T ATCACCAACAGCC ATAACAAAA Lys AGA Arg A ATG Met ACGAAGAGGG G GTT Val GCT Ala GAT Asp GGT Gly T GTCGCCGACGGCC GTAGCAGAA Glu GGAA GTGGCGGAGGGGG

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

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

11 3 billion base pair => 6 G letters & 1 letter => 1 byte The whole genome can be recorded in just 10 CD-ROMs! 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%!

12 Each Protein has a unique structure Amino acid sequence NLKTEWPELVGKSVEE AKKVILQDKPEAQIIVL PVGTIVTMEYRIDRVR LFVDKLDNIAEVPRVG 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 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

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.


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