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Fundamentals of Fundamentals of Protein StructureProtein Structure
August, 2006
Tokyo University of Science Tadashi Ando
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Our life is maintained by Our life is maintained by molecular network systemsmolecular 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 Proteins play key roles in a living systemliving 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 Amino acid: Basic unit of proteinprotein
COO-NH3+ C
R
HAn amino
acid
Different side chains, R, determin the properties of 20 amino acids.
Amino group Carboxylic acid group
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20 20 Amino acidsAmino acidsGlycine
(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 Proteins are linear polymers of amino acidsof 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+
H2OH2O
Peptide bond
Peptide bond
The amino acid sequence is called
as primary structure A AF
NGG
S TS
DK
A carboxylic acid condenses with an amino group with the release of a water
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Amino acid sequence is Amino acid sequence is encoded by DNA base encoded by DNA base sequence in a genesequence in a gene
・CGCGAATTCGCG・
・GCGCTTAAGCGC・
DNA molecule
=
DNA base sequence
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Amino acid sequence is Amino acid sequence is encoded by DNA base encoded by DNA base sequence in a genesequence in a gene
Second letterT C A G
Firs
t lette
r
T
TTTPhe
TCT
Ser
TATTyr
TGTCys
T
Th
ird le
tter
TTC TCC TAC TGC CTTA
LeuTCA TAA
StopTGA Stop A
TTG TCG TAG TGG Trp G
C
CTT
Leu
CCT
Pro
CATHis
CGT
Arg
TCTC CCC CAC CGC CCTA CCA CAA
GlnCGA A
CTG CCG CAG CGG G
A
ATTIle
ACT
Thr
AATAsn
AGTSer
TATC ACC AAC AGC CATA ACA AAA
LysAGA
ArgA
ATG Met ACG AAG AGG G
G
GTT
Val
GCT
Ala
GATAsp
GGT
Gly
TGTC GCC GAC GGC CGTA GCA GAA
GluGGA A
GTG GCG GAG GGG G
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Gene is protein’s Gene is protein’s blueprint, genome is life’s blueprint, genome is life’s
blueprint blueprint
Gene
GenomeDNA
Protein
Gene GeneGene
Gene
GeneGeneGeneGene
GeneGeneGeneGene
GeneGene
Protein Protein
ProteinProtein
Protein
ProteinProtein
Protein
Protein
Protein
Protein
ProteinProtein
Protein
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Gene is protein’s Gene is protein’s blueprint, genome is life’s blueprint, genome is life’s
blueprint blueprint Genome
Gene GeneGene
Gene
GeneGeneGeneGene
GeneGeneGeneGene
GeneGene
Protein Protein
ProteinProtein
Protein
ProteinProtein
Protein
Protein
Protein
Protein
ProteinProtein
Protein
Glycolysis network
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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 In 2003, Human genome sequence was sequence was deciphered!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%!
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Each Protein has a unique Each Protein has a unique structurestructure
Amino acid sequence
NLKTEWPELVGKSVEEAKKVILQDKPEAQIIVLPVGTIVTMEYRIDRVRLFVDKLDNIAE
VPRVGFolding!
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Basic structural units of Basic structural units of proteins: Secondary structureproteins: Secondary structure
α-helix β-sheet
Secondary structures, α-helix and β-sheet, have regular hydrogen-bonding patterns.
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Three-dimensional Three-dimensional structure of proteinsstructure of proteins
Tertiary structure
Quaternary structure
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Hierarchical nature of Hierarchical nature of protein structureprotein 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 Close relationship between protein structure and its protein structure and its
functionfunction
enzyme
A
B
A
Binding to A
Digestion of A!
enzyme
Matching the shape to A
Hormone receptor AntibodyExample of enzyme reaction
enzyme
substrates
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Protein structure prediction has Protein structure prediction has remained elusive over half a remained elusive over half a
centurycentury
“Can we predict a protein structure from its amino acid sequence?”
Now, impossible!
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SummarySummaryProteins 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.