Proteins and its function • Amino acids: building blocks ... - Nptel

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12/4/12 1 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 2

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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•  Derived from Greek “Proteios”

•  Linear polymers built of monomers (amino acids)

•  Most versatile macromolecules in living systems

•  Play key structural and functional roles

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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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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  

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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  

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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

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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  

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COO־  

Cα  

 

R

NH3  

H

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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  

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N  

C   Cα  

Cα  

H  

O  

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C  

O  

C  

N  

C  

H  

C  

O¯ˉ  

C  

N  +

C  

H  

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N  

C  

Cα  

H  

O  

Cα  

Trans  

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NC  

Cα  

H

O

Cα  

Cis  

Trans  

20  

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N

C   Cα  

Cα  

H  

OTrans  

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NC  

Cα  

O

Cα  

Cis  

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   4H2O  

Condensa5on  

Free  amino  acids  

Glycine   Alanine  

Valine  

Lysine  Primary  Structure  

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+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

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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  

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Ribbon diagram Ball and stick model

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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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•  α-Keratin

•  Two α helices wrap to form a stable structure

•  Collagen

•  It contains 3 helical polypeptide chain

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•  β sheets: another common, periodic structural motif

•  Fully extended structure •  Parallel •  Anti-parallel

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•  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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•  Three dimensional compactly folded structure of proteins

•  Overall organization of secondary structural elements in 3-D space

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•  Final level of protein structure

•  Spatial arrangement of subunits and their interactions

•  Polypeptide chains assemble to form multisubunit structure

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Individual polypeptide chains

Quaternary structure (Hemoglobin)

α- subunits

β- subunits

α

α

β

β

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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.