Introduction+to+Proteins+II


 * 22 August 2006**
 * Introduction to Proteins II**
 * Dr. Kandice Williams, Ph.D.**

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=**Primary Structure**=


 * Each protein has a unique amino acid sequence that defines its primary structure
 * Linking of amino acids in a linear polypeptide chain
 * α-carboxyl group of one amino acid is **covalently** linked to the α-amino group of another via peptide bond
 * The amino terminal end is the beginning of the polypeptide chain; carboxyl terminal end is the end of the polypeptide chain
 * Two amino acids linked together is called a dipeptide
 * Chain of more than two amino acids is called a polypeptide chain
 * All polypeptide chains are polar
 * Requires input of free energy (+21 kJ/mol) and loss of a water molecule to created a peptide bond
 * Requires +356 kJ/mol to break a peptide bond – very stable bond!

**Molecular Weight**

 * Molecular Weight (MW) is measured in Daltons which is equivalent to the atomic mass
 * **Average MW of one amino acid is 110 Daltons**
 * Most human proteins contain 50-2000 amino acid residues
 * MW would range between 5,500-220,000 Daltons

**Polypeptide Chain**

 * Polypeptide chain contains a peptide bond backbone and distinctive –R group side chains
 * Backbone always contains a carbonyl group, a good hydrogen bond receptor, an amine group (except for proline), and a good hydrogen bond donor
 * Backbone can interact with each other and with side chain functional groups
 * Disulfide bonds result in covalent cross-linking between and within proteins
 * -SH group forms disulfide bonds via oxidation
 * Two cysteine residues covalently bonded forms one cystine

**Peptide Bonds**

 * **Peptide bond is essentially planar** because of rigid double-bond-like characteristics
 * Peptide bond is uncharged, but is rich in hydrogen bond potential
 * For each pair of linked amino acids, there are 6 atoms within the same plane (amide plane)
 * Individual amino acids can be planar on their own individual amide plane
 * Planar peptide bonds can be in Trans or Cis configurations
 * Almost all peptide bonds are in **Trans** configuration because of steric hindrances in the Cis configuration
 * Amino acid linkages with proline causes steric hindrances in both configurations
 * Bonds in between peptide bonds have angles of rotation
 * phi (φ) is the angle of rotation between nitrogen of amino group and α-carbon
 * psi (ψ) is the angle of rotation between the α-carbon and the carbon atom of carbonyl group
 * Dihedral angle is the measure of rotation about each of the two single bonds – phi or psi
 * usually between -180° and +180°
 * Clockwise rotation is +
 * 3/4 of possible phi and psi combinations are excluded sterically
 * Using Ramachandron diagrams, the precise protein folding can be predicted in large polypeptide chains

=**Secondary Structure**=


 * Secondary structure is the special arrangement of amino acid residues along the polypeptide sequence
 * Primary amino acid predicts secondary structure
 * Predictions based on rigidity of peptide bond and restricted set of allowed phi and psi angles
 * Two basic periodic (regularly repeating) secondary structures: α-helix and β-pleated sheets.
 * Secondary structure can be predicted to an extent with different probabilities of a certain amino acid forming part of an α-helix, β-sheet, or reverse turn.

**α-Helix**

 * α-Helix consist of a tightly coiled backbone with side chains extending outwards
 * Essentially all α-helixes in proteins are right-handed (clockwise) to reduce steric hindrance between –R groups and backbone
 * α-Helix is 1.5 Å wide with 3.6 residues per 360° turn
 * N-H group and C=O hydrogen bonds to stabilize secondary structure with bonds distributed 4 residues apart such that **all** backbone N-H and C=O groups are bonded
 * α-Helix are very strong and several helixes can super coil with each other to further enhance strength

**β-Pleated Sheets**

 * β-pleated sheets are more extended and looser in a zigzag structure
 * Adjacent amino acids are stretched 3.5 Å apart
 * Side chains are above and below the peptide bond
 * β-sheets are formed by linking two or more β-strands by hydrogen bonds
 * Can link parallel head to head (with amino terminal ends lined up) or anti-parallel head to tail (with amino terminal lined up with carbonyl terminal)
 * Parallel β-sheets hydrogen bond staggered between amino acids on opposite strand
 * Anti-parallel β-sheets hydrogen bond directly with amino acids on opposite strand
 * Amino acids can have both parallel and anti-parallel structure in the same protein
 * β-sheets can adopt a “flat and twisted” shape

**Reverse Turns**

 * Reverse turns that compact protein structures are not periodic but rigid
 * Often found on surface of protein and can interact between protein and other molecules
 * Most common structural element is the reverse turn (β-turn, hairpin loop)
 * C=O group of residue i hydrogen bonds with N-H group of residue i+3
 * Omega loops are more elaborate structures responsible for chain reversals

=**Objectives**=