Download What amino acids really look like

What amino acids really look like
Tetrahedral carbon Cα
Page 13 (12)
Molecular Asymmetry
Page 18 (16)
Chiral
Achiral
Carbon with 4 different
substituent groups (hand)
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
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
The Polypeptide chain
Amino
terminus
NH2
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
Polypeptide chain
Page 119 (116)
Unique sequences:
= (number of possible amino acids) (amino acid length)
204 =160,000
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
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
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
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 180o in very
nearly all of the main chain peptide bonds. In rare cases ω = 0o
for a cis peptide bond which usually involves proline
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.
(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
Protein Folding
Concept of protein folding energy well
Many weak interactions
Only 10 KJmol-1
differentiates a folded
functional to a
precipitated protein
Noncovalent Interactions between amino
acids (in a folded protein)
Hydrogen bond
(~4.0-40.0 KJmol-1)
Hydrophobic interactions
(~0.4-4.0 KJmol-1)
Π bonding
(~0.4-4.0 KJmol-1)
Van der Waals interactions
(~0.4-4.0 KJmol-1)
Electrostatic
(~4.0-40.0 KJmol-1)
Salt bridge
(~40.0-400.0 KJmol-1)
-CH2-OH ………O-CH donor/acceptor
displacement of water
aromatic amino acid stacking
weak (but many)
pH effect/repulsion
Asp, Glu (carboxyl side chain)
Arg, Lys (basic side chain)
Hydrogen bond
Polar amino acids
Trp
Phe
Trp
Charged amino acids
Simple rule:
If pH of environment less than
pKa 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
Disulfide Bridge
When two cysteine are close to each other in the folded protein
(important in protein folding)
-CH2-SH +
HS-CH22H+ + 2e(oxidation/
reduction)
-CH2-S-S-CH2 (oxidized)
Forms a covalent bond
(~200-800.0 KJmol-1)
Free rotation about S-S bond
Stabilizes the 3 dimensional structure
Example of a protein with disulfide bond
Summary