Part 1 espyr1 S31 ProteinsI

LSM1401 Summary Notes (3a) © Lim Fang Jeng

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Proteins Structure & Functions

Amino Acids

- They are the building blocks for proteins (20 common types) - Consists of

o Amino group NH2

o Carboxyl group COOH

- -amino acids – the amino acids with NH2 group on carbon adjacent to COOH group - Protein-derived amino acids

o At least one stereocentre ( -carbon) o They are chiral

o Glycine does not have the property of chirality due to the structure - L and D- Amino acids

o Determined by the left and right of the NH³⁺ group in fischer projection

Protein-derived Amino Acids

- All are - amino acids and being classified by their R-side chains

o Non-Polar side chains (Leucine, Proline, Alanine, Valine, Methionine, Tryptophan, Phenylalanine, Isoleucine)

o Polar side chains

 Charged

 Acidic ( Aspartic acid, Glutamic acid)

 Basic (Histidine, Lysine, Arginine)

 Uncharged ( Glycine, Serine, Asparagine, Glutamine, Thereonine, Cysteine, Tyrosine) - Examples for Non-polar amino acids

o Proline

 Consists of secondary amino group (-NH-)

 Has cyclic structure (effective in stopping amino chain growth)

 Known as imino acid - Examples for Polar amino acids

o Glycine (Uncharged)

 Achiral (The ONLY achiral protein-derived amino acid)

 No stereocentre

 Smallest amino acids (found in the internal loop of -helix) o Cysteine (Polar uncharged)

 Consists of S-H group

 Form disulphide bond with another cysteine molecule to form Cystine

 It is important in holding proteins together by disulphide bond o Histidine (Basic)

 R group: Imidazole (pK^a=6.0)

 Important biological buffers - Uncommon Amino acids

o After Post-translational modification Eg, by addition of chemical groups o Example: hydroxyproline, hydroxylysine, thyroxine

LSM1401 Summary Notes (3a) © Lim Fang Jeng

2

Ionisation of Amino Acids

- _pKa of Amino group = 2.0- 2.4 (Acidic) - _pKa of carboxyl group= 9.0-9.8 (Alkaline) - Nonionic form – no charge

- Zwitterionic form – Neutral charge (NH^{3+ and COO-} balanced out) - At physiological pH (~7.4)

o Amino group is protonated (NH^{2 to NH3+)} o COOH group is deprotonated (COOH to COO^-) o Zwitterion

- At low pH (more H⁺⁾

o Amino group & COOH group are protonated o Net positive charge

- pH increasing

o COOH group starts deprotonate o No net charge

- At high pH (less H⁺⁾

o Amino group deprotonated o Net negative charge (COO^-)

- Isoelectric point (pH at which Zwitterion is formed)

o For non-ionisable amino acids: pI =¹₂ pK1^{+ pK}2 o For ionisable side chains:

 There are 3 pK^{a values}

 Choose the two which involve the neutral form

Peptide Bond

- Amide bond between -carboxyl group and -amino group of two amino acids - No rotation around peptide bond, they formed an amide plane

- It has a property of partial double bond Peptides are written from left to right

- Begin: free -NH^{3+ group} - End: free -COO^{- group}

Protein Structure

Primary Structure

- Sequence of amino acids in a polypeptide chain - Important in determining three-dimensional structure

Secondary Structure

- A section of a 3-D chain results by the hydrogen bond interaction of the peptide backbone

Angles between C _{− N: ϕ} Angle between C _{− C: ψ}

- The planes can rotate freely, NOT PEPTIDE BONDS!

Use these two to calculate pI

LSM1401 Summary Notes (3a) © Lim Fang Jeng

3

- -Helix

o Right handed coil o 3.6 amino acids per turn

o Pitch = 5.4 Å = ^{. × −�}� ^(0.54nm) o Stabilised by internal hydrogen bonds

 O atom of C=O bond and H atom of N-H group bond together 4 residues away

 Hydrogen bonds parallel to helical axis

o R groups of amino acid residues point outward from the helix

o Disruption factors

 Proline

 Cyclic structure restricting rotations

 Missing H on the NH³⁺ for hydrogen bonding

 Strong electrostatic repulsion

 Caused by near repulsion of two same charged amino acids

 Lys and Arg; Glu and Asp

 Steric crowding

 Caused by near of BULKY SIDE CHAINS

 The helix cannot fold

 Val, Ile, Thr - -sheet

o Polypeptide chains lie adjacent to one another

o R groups of the adjacent amino acid residues protrudes out of the sheet in opposite directions

o Two kinds:

 Antiparallel

 Parallel

o C=O and N-H groups of each peptide bond are perpendicular to the axis of the sheet

o The hydrogen bonds lies on the plane and perpendicular to the direction of the sheet

 Gives a pleated (zig-zag) structure

Small Peptides

- L-Aspartyl L-phenylalanine (Aspartame) o Acts as a non-sugar sweetener