Download lecture5lifes_chemical_basis

16th August 2013
carbohydrates, lipids, proteins and nucleic acids
“Molecules of life”
Packets of instantly available energy
Energy stores
Structural material
Metabolic workers
Libraries of hereditary information
Cell to cell signals
Slides by : J Sen
Proteins are communication devices to conduct
biological processes
Proteins
Enzymes – that
carry out
chemical
reactions are
largely proteins.
How are Proteins made?
DNA
Transcription
RNA
Most drugs bind
to proteins to
repair a ‘faulty
bio-machine’ to
restore order in
the system
(organism).
Translation
Protein
Cellular processes
Most drugs bind to proteins to repair
a ‘faulty bio-machine’ to restore order
in the system (organism).
HIV drugs that bind to a target
protein exploits shape
complementarity
Viruses infect by manipulating their proteins
Isolated Viral Capsid protein
Fully formed stable virus particle
Proteins play crucial roles in all biological processes
Trypsin, Chmytrypsin – enzymes
Hemoglobin, Myoglobin – transports oxygen
Transferrin – transports iron
Ferritin – stores iron
Myosin, Actin – muscle contraction
Collagen – strength of skin and bone
Rhodopsin – light-sensitive protein
Acetylcholine receptor – responsible
for transmitting nerve impluses
Antibodies – recognize foreign substances
Repressor and growth factor proetins
Slides by : Sankar
Biopolymers
Proteins
Building Blocks
Proteins Amino acids
Nucleic acids Enzymes carryNucleotides
out these
Carbohydrates reactions. Sugars
Lipids
Fatty acids
Proteins talk to each other due to shapecomplementarity.
The shape is important for its function.
Proteins are polymers of amino acids
Proteins are made up of 20 amino acids
– a very small tool kit!!
NH2
H
C
COOH
R
R varies in size, shape, charge, hydrogen-bonding
capacity and chemical reactivity.
Slides by : Sankar
Only L-amino acids are constituents of proteins
Slides by : Sankar
Nonpolar and hydrophobic
Basic
Acidic
Slides by : Sankar
20 amino acids are linked into proteins by
peptide bond
Slides by : Sankar
Peptide bond has partial double-bonded
character and its rotation is restricted.
Slides by : Sankar
Polypeptide backbone is a repetition of basic
unit common to all amino acids
Slides by : Sankar
YGGFL is a different polypeptide than LFGGY
Slide by : J. Sen
A
Ala
alanine
C
Cys
cysteine
D
Asp
aspartic acid
E
Glu
glutamic acid
F
Phe
phenylalanine
G
Gly
glycine
H
His
histidine
I
Ile
isoleucine
K
Lys
lysine
L
Leu
leucine
M
Met
methionine
N
Asn
asparagine
P
Pro
proline
Q
Gln
glutamine
R
Arg
arginine
S
Ser
serine
T
Thr
threonine
V
Val
valine
W
Trp
tryptophan
Y
Tyr
tyrosine
Large proteins sequence lengths are
long.
One letter code is
easier to work with than
the three-letter codes
for amino acids.
Slide by : Sankar
Proteins
Long polymers : from 20 amino acids
Primary structure
ADDFGFIPRELALKRMKGSTPNY
Fold into compact
structures
Protein Structure: Four Basic Levels
Primary Structure
Secondary Structure
Tertiary Structure
Quaternary Structure
Slides by : Sankar
Slides by : Sankar
An educated guess of the proteins function
from the primary sequence
Histone (human)
SETVPPAPAASAAPEKPLAGKKAKKPAKAAAASKKKPAGPSVSELIVQAASSSKE
RGGVSLAALKKALAAAGYDVEKNNSRIKLGIKSLVSKGTLVQTKGTGASGSFKLN
KKASSVETKPGASKVATKTKATGASKKLKKATGASKKSVKTPKKAKKPAATRKS
SKNPKKPKTVKPKKVAKSPAKAKAVKPKAAKARVTKPKTAKPKKAAPKKK
Rhodopsin (human)
MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPI
NFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTG
CNLEGFFATLGGEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVM
ALACAAPPLAGWSRYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIF
FCYGQLVFTVKEAAAQQQESATTQKAEKEVTRMIIMVIAFLICWVPYASVAFYIFT
HQGSNFGPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDE
ASATVSKTETSQVAPA
How does a protein’s three dimensional
structure emerge?
The primary structure of the protein gives rise to the protein’s
shape in the following ways:
1) It allows hydrogen bonds to form between the C=O and N-H
groups of different amino acids along the length of the
polypeptide chain.
2) It puts “R” groups into positions that allow them to interact.
Through their interactions the chain is forced to bend and
twist.
Slide by : J. Sen
The anatomy of the peptide backbone
The peptide bond is essentially plannar
These atoms are on the same plane.
Slide by : J. Sen
Second level of protein structure
Hydrogen bonds form at short intervals along the new polypeptide chain
and they give rise to a coiled or extended pattern known as the secondary
structure of the protein.
Think of the polypeptide
chain as a set of rigid
playing cards joined by
links that can swivel a bit.
Each card is a peptide
group.
Atoms on either side of it
can rotate slightly around
their covalent bonds and
form bonds with
neighboring atoms.
Slide by : J. Sen
Alpha helix (α helix)
Features:
1. It is a rod like structure.
2. Backbone is inside while
side chains are on the
outside.
3. Hydrogen bonding between
CO and NH groups of the
main chain stabilizes the
structure.
4. CO group of residue R
hydrogen bonds with the NH
group of residue R+4.
5. Rise per residue is 1.5Å and
rotation per residue is 100
degrees, therefore, residues
per turn is 3.6.
6. Most α-helices observed
naturally are right-handed
helices.
Slide by : J. Sen
Pauling and Corey predicted the structure of α-helix 6 years before it was actually experimentally
observed for the structure of Myoglobin.
The elucidation of the structure of α-helix is a landmark in
Biochemistry because it was demonstrated that the conformation of
a polypeptide chain can be predicted if the properties of its
constituents are rigorously and precisely known.
For this work Pauling got the Nobel prize in Chemistry in 1954.
The helical content of a protein may vary anywhere between 0% to 100%.
75% of AAs in Ferritin, an iron storage protein is in alpha-helices.
α-helices are usually less than 45Å long. However, two or more α-helices can entwine to form a very
stable structure, which can have a length of 1000Å or more. Such α-helical coiled coils are found in
many structural proteins e.g. myosin, tropomyosin in muscle, Fibrin in blood, Keratin in hair etc.
α-helical
coiled coil
Slide by : J. Sen
Beta sheet (β sheet)
Where residues per turn is 2 (n=2) it is a β-pleated sheet structure. There are two kinds of βpleated sheet structures either the chains (strands) are such that in two successive chains
they have same directionality for N>C or they are parallel chains (parallel β-sheet) or they are
in opposite/ anti-parallel orientation (anti-parallel β-sheet).
Features:
1. Distance between two successive amino acids is
3.5Å.
2. The side chains are at 180° to each other.
3. Adjacent β-strands are linked by hydrogen
bonds.
4. In antiparallel β-sheets the hydrogen bonds
between the CO and NH of adjacent strands
form between groups that are diametrically
opposite to each other.
5. In parallel β-sheets hydrogen bonds between
CO group of one amino acids forms with the NH
group of two amino acids downstream in the
other strand.
Slide by : J. Sen
6. β-strands are depicted by arrows schematically.
β-sheet is an important structural element in many proteins e.g. fatty-acid binding proteins, important for lipid
metabolism, are almost exclusively built of β-sheets.
Many β-strands (4-10 or more) may come together in a protein. These β-strands may be all parallel to each other
or anti-parallel or mixed.
A and B are ball and stick and ribbon model of the same polypeptide, respectively. β-strands may have twists.
Side view of the schematic in B demonstrates the twists.
A protein rich in β-sheets,
This is a fatty acid binding protein – but not necessary
that all fatty acid binding proteins are like this.
Slide by : J. Sen