16th August 2013

carbohydrates, lipids, proteins and nucleic acids

“Molecules of life”

Packets of instantly available energy

Energy storesStructural materialMetabolic workersLibraries of hereditary information

Cell to cell signals

Slides by : J Sen

Proteins are communication devices to conduct biological processes

How are Proteins made?

DNA

RNA

Protein

Cellular processes

Transcription

Translation

Proteins

Enzymes – that carry out chemical

reactions are largely proteins.

Most drugs bind to proteins to

repair a ‘faulty bio-machine’ to restore order in

the system (organism).

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 processesTrypsin, Chmytrypsin – enzymes

Hemoglobin, Myoglobin – transports oxygenTransferrin – transports ironFerritin – stores iron

Myosin, Actin – muscle contraction

Collagen – strength of skin and bone

Rhodopsin – light-sensitive proteinAcetylcholine receptor – responsible for transmitting nerve impluses

Antibodies – recognize foreign substancesRepressor and growth factor proetins

Slides by : Sankar

Biopolymers Building Blocks

Proteins Amino acidsNucleic acids NucleotidesCarbohydrates SugarsLipids Fatty acids

Proteins

Enzymes carry out these reactions.

Proteins are polymers of amino acids

Proteins talk to each other due to shape-complementarity.

The shape is important for its function.

Proteins are made up of 20 amino acids

NH2

H C COOHR

R varies in size, shape, charge, hydrogen-bonding capacity and chemical reactivity.

Slides by : Sankar

– a very small tool kit!!

Only L-amino acids are constituents of proteins

Slides by : Sankar

Nonpolar and hydrophobic

AcidicBasic

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 alanineC Cys cysteineD Asp aspartic acidE Glu glutamic acidF Phe phenylalanineG Gly glycineH His histidineI Ile isoleucineK Lys lysineL Leu leucineM Met methionineN Asn asparagineP Pro prolineQ Gln glutamineR Arg arginineS Ser serineT Thr threonineV Val valineW Trp tryptophanY 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

Long polymers : from 20 amino acids

Fold into compact structures

Primary structure ADDFGFIPRELALKRMKGSTPNY

Proteins

Protein Structure: Four Basic Levels

Primary Structure

Secondary Structure

Tertiary Structure

Quaternary Structure

Slides by : Sankar

Slides by : Sankar

SETVPPAPAASAAPEKPLAGKKAKKPAKAAAASKKKPAGPSVSELIVQAASSSKERGGVSLAALKKALAAAGYDVEKNNSRIKLGIKSLVSKGTLVQTKGTGASGSFKLNKKASSVETKPGASKVATKTKATGASKKLKKATGASKKSVKTPKKAKKPAATRKSSKNPKKPKTVKPKKVAKSPAKAKAVKPKAAKARVTKPKTAKPKKAAPKKK

Histone (human)

MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGGEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSRYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVKEAAAQQQESATTQKAEKEVTRMIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDEASATVSKTETSQVAPA

Rhodopsin (human)

An educated guess of the proteins function from the primary sequence

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

These atoms are on the same plane.

The peptide bond is essentially plannar

Slide by : J. Sen

Second level of protein structureHydrogen 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 β-pleated 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.

6. β-strands are depicted by arrows schematically.Slide by : J. Sen

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