What amino acids really look like

Transcription

1 What amino acids really look like

2 Tetrahedral carbon Cα Page 13 (12)

3 Molecular Asymmetry Page 18 (16) Chiral Carbon with 4 different substituent groups (hand) Achiral

4 Amino acid Structure The central carbon (Cα-atom) is a chiral center Encoded proteins have the L-configuration at this chiral center Configuration can be remembered as the CORN law Looking along the H-Cα bond with H atom closest to you Reading clockwise, the groups attached to the Cα spell CORN

5 Peptide Bond All amino acids have amino and carboxyl groups When an amino acid is incorporated into a polypeptide by the ribosome at position i in the sequence, it undergoes a condensation reaction in which the carboxyl group of the preceding amino acid (i-1) forms an amide (or peptide) bond with the amino group residue i. In the next elongation cycle of the ribosome, the carboxyl group of residue i becomes covalently linked to the amino group of residue i+1 in the final sequence by another peptide bond

6 The Polypeptide chain Amino terminus NH 2 Carboxyl terminus HOOC Amino acids in proteins (or polypeptides) are joined together by peptide bonds and have different properties: acidic, basic, neutral, hydrophobic, etc (see L5) The amino acid side-chains also direct the folding of the nascent polypeptide and stabilize its final conformation

7 Polypeptide chain Page 119 (116)

8 Unique sequences: = (number of possible amino acids) (amino acid length) 20 4 =160,000

9 Primary structure: the sequence of amino acids along the chain Secondary structure: the local folding of the polypeptide chain Tertiary structure: the arrangement of secondary structure elements in 3 dimensions Quaternary structure: the arrangement of proteins forming a function unit Amino acids confer important properties on the protein such as the ability to bind ligands and catalyze biochemical reactions

10 Peptide Bond Structure Linus Pauling and Robert Corey analyzed the geometry and dimensions of the peptide bonds in the crystal structures of molecules containing one or a few peptide bonds Summary: The consensus bond lengths are shown in Angstrom units Bond angles in degrees are also shown for the peptide N and C atoms

11 Note that the C-N bond length of the peptide is 10% shorter than that found in usual C-N amine bonds. This is because the peptide bond has some double bond character (40%) due to resonance which occurs with amides. The two canonical structures are: As a consequence of this resonance all peptide bonds are found to be almost planar, i.e. atoms, C(i), O(i), N(i+1) and H(i+1) are approximately co-planar. This rigidity of the peptide bond reduces the degrees of freedom of the polypeptide during folding

12 Peptide Torsion Angles The three main chain torsion angles of a polypeptide are: phi, psi and omega. The planarity of the peptide bond restricts ω to 180 o in very nearly all of the main chain peptide bonds. In rare cases ω = 0 o for a cis peptide bond which usually involves proline

13 cis and trans configuration The peptide bond nearly always has the trans configuration since it is more favorable than cis, which is sometimes found to occur with proline residues. Steric hindrance between the functional groups attached to the Cα atoms will be greater in the cis configuration.

14 (trans) However for proline residues, the cyclic nature of the side chain means that both cis and trans configurations have more equivalent energies. Thus proline is found in the cis configuration more frequently than other amino acids. The omega torsion angle of proline will be close to zero degrees for the cis configuration, or most often, 180 degrees for the trans configuration

15 Protein Folding

16

17 Concept of protein folding energy well

18 Many weak interactions Only 10 KJmol -1 differentiates a folded functional to a precipitated protein

19 Noncovalent Interactions between amino acids (in a folded protein) Hydrogen bond -CH 2 -OH O-C- (~ KJmol -1 ) H donor/acceptor Hydrophobic interactions displacement of water (~ KJmol -1 ) Π bonding aromatic amino acid stacking (~ KJmol -1 ) Van der Waals interactions weak (but many) (~ KJmol -1 ) Electrostatic ph effect/repulsion (~ KJmol -1 ) Salt bridge Asp, Glu (carboxyl side chain) (~ KJmol -1 ) Arg, Lys (basic side chain)

20 Hydrogen bond

21

22 Polar amino acids

23

24 Trp Phe

25 Trp

26

27

28 Charged amino acids

29

30 Simple rule: If ph of environment less than pk a amino acid + charge If ph of environment greater than pka amino acid - charge Examples: Arg at ph 7.4 Arg pka 12.5 (ph less than pka) + charge Asp at ph 7.4 Asp pka 3.9 (ph greater than pka) - charge

31 Disulfide Bridge When two cysteine are close to each other in the folded protein (important in protein folding) -CH 2 -SH + HS-CH 2-2H + + 2e - (oxidation/ reduction) -CH 2 -S-S-CH 2 (oxidized) Forms a covalent bond (~ KJmol -1 ) Free rotation about S-S bond Stabilizes the 3 dimensional structure

32 Example of a protein with disulfide bond

33

34 Summary