Proteins and its function • Amino acids: building blocks ... - Nptel
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Transcript of Proteins and its function • Amino acids: building blocks ... - Nptel
12/4/12
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Dr. Sanjeeva Srivastava IIT Bombay
IIT Bombay Proteomics Course NPTEL
• Proteins and its function
• Amino acids: building blocks
• Different levels of protein structure
• Primary, Secondary, Tertiary, Quaternary
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IIT Bombay Proteomics Course NPTEL 3
• Derived from Greek “Proteios”
• Linear polymers built of monomers (amino acids)
• Most versatile macromolecules in living systems
• Play key structural and functional roles
IIT Bombay Proteomics Course NPTEL 4
Prom
oter T
A T A
C A G
T A C
C G T
Q
Y
R
Message
DNA Sequence
Protein Sequence & Regula5on
Protein Structure
Protein/ Enzyme Structure
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IIT Bombay Proteomics Course NPTEL 5
Protein Functions
SIGNALLING
TRANSPORT
CATALYSIS
MOVEMENT
STRUCTURE
REGULATION
Off
On
Α
Β
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Glycine
H N C H
H
COO
+
3
-‐ -‐
CH2
CH2
COO
C H
H N +
2
H2C
Proline Alanine
COO
H N C H
CH3
+
3
-‐ COO
H N C H
CH
+
3
-‐
CH 3 CH 3
Valine
COO
H N C H
CH2
+
3
-‐
CH 3 CH 3
CH
Leucine
-‐ COO
H N C H
C
CH3
+
3
H CH 3
CH2
Isoleucine
COO
H N C H
CH2
+
3
-‐
CH 3
CH2
S
Methionine IIT Bombay Proteomics Course NPTEL 7
H N C H
CH2OH
COO +
3
-‐
Serine
COO
+
3
-‐
CH3
H OH
Threonine
COO +
3
-‐
SH
Cysteine
COO
H N C H
CH2
+
3
-‐
H N 2 O
C
Asparagine
COO
H N C H
CH2
+
3
-‐
H N 2 O
CH2
C
Glutamine
H N C H
C
H N C H
CH2
IIT Bombay Proteomics Course NPTEL 8
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COO
H N C H
CH2
+
3
-‐
CH 2
CH2
CH2
NH3 +
COO
H N C H
CH2
+
3
-‐
NH
CH2
CH2
NH2
C
NH2 +
Lysine Arginine
COO
H N C H
CH2
+
3
-‐
C
C
NH
CH
N H
His5dine
IIT Bombay Proteomics Course NPTEL 9
COO
H N C H
CH2
+
3
-‐
COO -‐
Aspartate
COO
H N C H
CH2
+
3
-‐
CH 2
COO -‐
Glutamate
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COO
H N C H
CH2
+
3
-‐
Phenylalanine
COO
H N C H
CH2
+
3
-‐
OH
Tyrosine
COO
H N C H
CH2
+
3
-‐
C CH
NH
Tryptophan
Hydrophilic Hydrophobic
Hydrophobic character
IIT Bombay Proteomics Course NPTEL 11
Wavelength (nm)
Exti
ncti
on c
oeff
icie
nt
220 240 260 280 300 320
10,000
8,000
6,000
4,000
2,000
0
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COO־
Cα
R
NH3
H
COO־
Cα
R
NH3
H
L-‐Isomer D-‐Isomer
IIT Bombay Proteomics Course NPTEL 13
IIT Bombay Proteomics Course NPTEL 14
COO־
Cα
R
NH3
H
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IIT Bombay Proteomics Course NPTEL 15
C
H R
+ H3N C
HR
+ H3N C
R H
+ H3N
0 2 4 6 8 10 12 14
Zwitterionic Form
Both groups Protonated
Both groups Protonated
C C N
R2
+ C
N C
R1
+
IIT Bombay Proteomics Course NPTEL
R1
C
+H3N C
O
N
H
C
R2 H
+ H20
H
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N
C
H
O
C
R1
H
N
C
C
O H
R2 H
N
C
H
O
C
R3
H
N
C
C
O H
R4 H
Backbone
IIT Bombay Proteomics Course NPTEL 17
N
C Cα
Cα
H
O
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C
O
C
N
C
H
C
O¯ˉ
C
N +
C
H
IIT Bombay Proteomics Course NPTEL 19
N
C
Cα
H
O
Cα
Trans
IIT Bombay Proteomics Course NPTEL
NC
Cα
H
O
Cα
Cis
Trans
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N
C Cα
Cα
H
OTrans
IIT Bombay Proteomics Course NPTEL
NC
Cα
O
Cα
Cis
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4H2O
Condensa5on
Free amino acids
Glycine Alanine
Valine
Lysine Primary Structure
IIT Bombay Proteomics Course NPTEL 23
+H3N
C
H2C
O
C
N
C
C
O H
H
N
C
H
O
C
H
N
C
C
O H
H2C H
H H
N
C
H2C
C
H
H
_
HC
CH3
CH3
H
OH
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• Essential for elucidation of its mechanism of action
• Determines 3-D structure of proteins
• Amino acid alteration can produce abnormality
• Sequence tells us an evolutionary history of protein
IIT Bombay Proteomics Course NPTEL 26
Cα
C
Cα C
H
H
O
N
N
H
H H
R1 R3
R2
Cα
Ψ
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-‐180 -‐150 -‐120 -‐90 -‐60 -‐30 0 30 60 90 120 150 180 -‐180
-‐15
0 -‐1
20 -‐90 -‐6
0 -‐30 0 30 60
90 120
15
0 180
Psi
Phi Ψ
= 90°, Ψ = - 90° IIT Bombay Proteomics Course NPTEL 27
IIT Bombay Proteomics Course NPTEL 28
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Ribbon diagram Ball and stick model
IIT Bombay Proteomics Course NPTEL 29
N C
H
O
C
Ri
H
N C
C
O H
Ri+1 H
N C
O
C
H
N C
C
O H
Ri+3 H
H Ri+2
N C
O
C
H
N C
C
O H
Ri+5 H
H Ri+4
Residue i (CO) ____________i + 4 (NH)
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IIT Bombay Proteomics Course NPTEL 31
• α-Keratin
• Two α helices wrap to form a stable structure
• Collagen
• It contains 3 helical polypeptide chain
IIT Bombay Proteomics Course NPTEL 32
• β sheets: another common, periodic structural motif
• Fully extended structure • Parallel • Anti-parallel
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IIT Bombay Proteomics Course NPTEL 33
• More elaborate structures loops or omega turns
• Loops are rigid, no periodic structures
• Turns and loops on surfaces
• Participate in protein and other molecule interactions
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α helix β sheets
Rod like structure Sheet like structure
Axial distance 1.5 A Axial distance 3.5 A
Polypeptide chain tightly coiled
Polypeptide chain fully extended
H-bond between NH and CO groups in same polypeptide chains
H-bond between NH and CO groups in different polypeptide chains
Examples – Ferritin, keratin, collagen
Fatty acid binding protein
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IIT Bombay Proteomics Course NPTEL 36
• Three dimensional compactly folded structure of proteins
• Overall organization of secondary structural elements in 3-D space
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IIT Bombay Proteomics Course NPTEL 38
• Final level of protein structure
• Spatial arrangement of subunits and their interactions
• Polypeptide chains assemble to form multisubunit structure
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IIT Bombay Proteomics Course NPTEL 39
Individual polypeptide chains
Quaternary structure (Hemoglobin)
α- subunits
β- subunits
α
α
β
β
IIT Bombay Proteomics Course NPTEL 40
DNA Genetic blueprint
RNA molecular photocopy
Proteins Building blocks
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IIT Bombay Proteomics Course NPTEL
• Proteins and its function
• Amino acids: building blocks • Different levels of protein structure
• Primary, Secondary, Tertiary, Quaternary
• Myoglobin and Hemoglobin
• Proteins and diseases
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IIT Bombay Proteomics Course NPTEL
• Berg J., Tmyoczko J. & Stryer L., Biochemitry fifth ed., W. H. Freeman & company, 2002. ISBN: 0716746840. • Nelson D. & Cox M.,Lehninger, Principles of Biochemistry fourth ed., W. H. Freeman and company, 2004. . ISBN: 023022699X. • Voet D. & Voet J., Biochemistry fourth ed., Wiley, 2000. ISBN: 047158651X.