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Nucleic Acids
Two classes of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid
(RNA)
Cells use DNA to determine and control the synthesis of proteins with the help
of mRNA.
Ka = 107
MeCOOH
Ka = 1.74 x 10-5
This is to do with the strength (stability) of the conjugate base, Cl- is not strong enough to
deprotonate H3O+, but acetate is. In other words, the chloride ion is inherently more stable than
the acetate ion.
An acids pKa depends on the stability of its conjugate base.
- The stronger the acid HA, the weaker its conjugate base A- The stronger the base A-, the weaker the conjugate acid HA.
For example:
- HI with pKa of -10, is a strong enough acid to protonate most functional groups. Its conjugate
base, I- is not really basic.
- Methyl lithium is a powerful base, which behaves as CH3-. The conjugate acid is CH4, which isnt
acidic with pKa = 48.
Peptide Bond Formation
Condensation rxn Between NH2 of n residue and COOH of n+1 residue. Rigid, inflexible.
Loss of 1 water molecule.
The peptide bond has a barrier to rotation. The resonance structure explains this, and bond length
comparisons are consistent with partial double bond character. As a consequence, the atoms are all
constrained to lie in the same plane. The peptide bond is planar. But the planar conformation can be
accommodated in two alternate forms denoted as trans and cis. The more stable trans form. The
cis form is less stable because of its greater steric repulsion between the C atoms and their
attached groups.
Peptides and Proteins
Peptides and protein made up from long chains of amino acids via peptide bonds.
There are two types of protein structures: fibrous (elongated proteins not soluble in water and
providing structural support), and globular (spherical proteins soluble in water and have specific
function in the immune system and metabolism).
The structural proteins
Primary Structure The sequence of amino acids The peptide bond is rigid and can not move due
to its partial double bond character of C-N bond. To write peptide and protein always from Nterminal to C-terminal.
Secondary Structure Regular elements such as -helices and - sheets, which are formed
between relatively small parts of the protein sequence. They are determined by the local
conformation of the polypeptide backbone. -helix Most abundant; ~35% of residues in a protein
Repetitive secondary structure 1.5 rise in 100 rotation C=Oof i forms H bonds with N-H of
residue i+4 Intra-strand H bonding C=O groups are parallel to the axis; side chains point away
from the axis Polar ends present at surfaces Amphipathic All N-H and CO are H-bonded, except
first N-H and last CO
-sheet
Other major structural element Basic unit is a -strand Usually 5-10
Residues Can be parallel or anti-parallel based on the relative directions
of interacting -strands Pleated appearance
Another important interaction is the formation of hydrogen bonds
between the carbonyl oxygen and amide hydrogens on adjacent regions
of the peptide backbone:
-sheet (with primary structure)
(a) antiparallel and (b) parallel -sheet. Blue and white
beads represent the positively charged (Arg) and
hydrophobic residues, respectively, and the polar
residue (Tyr) and Gly residues are denoted by green
beads. Solid lines indicate the disulfide bonds between
Cys residues, and dotted lines indicate the backbone
hydrogen bond (H-bond).
-pleated sheet
The chains are folded so that they lie alongside each other. All that means is that next-door chains
are heading in opposite directions. Given the way this particular folding happens, that would seem
to be inevitable.
The generalized structure of an amino acid: Amino acids are chiral
Some of the amino acids have hydrophobic side chains; others have hydrophilic side chains. The
molecules (can exist as right or left handed forms). But whereas in the case of
different AA like to interact with each other, and the protein chain folds to maximize these
sugar, the right-handed form predominates in cells, in the case of amino acids, it interactions. Also one important way a protein folds is such that the hydrophobic AA will be in the
is the left-handed form that is found in cells.
interior of the folded protein, and the hydrophilic AA will be on the surface. In addition to the
Amino Acids
backbone hydrogen bonds that permit the formation of secondary structures, other interactions
Names for amino acids are abbreviated to either three symbol or a one symbol between the side chains of the various AA govern the overall the folded structure of the protein.
short form.
20 amino acids found in living organisms.
Building blocks of peptide and protiens
Linear chain of amino acids forms peptide/protein.
Peptides - Small peptides with fewer than about ten amino acids are called
oligopeptides
and peptides with more than ten amino acids are termed polypeptides.
Proteins Chain of amino acids with molecular weights of more than 10,000
(50100 amino acids) are usually termed proteins.
R group varies, thus, can be classified based on R-group.
Glycine is the simplest amino acid. Side chain R=H.
Unique because Gly -carbon is achiral.
Chiral: when a molecule is not superimposable on its mirror image
Zwitterionic character, pK and pI
Tertiary Structure
At the pH under physiological conditions (pH 6-7), the amino group (pK
Describe the complete three-dimensional structure of whole polypeptide chain. Include the
8.7~10.7) is ionized to NH3+ and the carboxyl group (pK 1.8~2.5) is ionized to relationship of different domains formed by the proteins secondary structure and the interactions
COO-. So, at physiological pH,. amino acids are zwitterionic
Level
Description
Stabilized by:
of the amino
acid substituent R group.
pK is the dissociation constant for H+.
Primary
The sequence
amino acids
Peptide bondsstable within a restricted range of
The specific
folding of of
a protein
is only thermodynamically
pI (isoelectric point) - It is a specific pH value at which aa exhibits no net
Secondar
Formation
of a-helices
b-pleated H-bonding
between
peptide groups along the peptide
environmental
parameters,
e.g.,and
Temperature,
pH, ionic
strength
charge.
yQuaternary
sheets
backbone
Structure
It can be estimated via the Henderson- Hasselbalch equation pI = (pKNH3+
Tertiary
Overall
three-dimensional
shape arrangement
Bonds and other
interactions
Quaternary
structure
is the 3-Dimensional
of multiple
folded between
protein orR-groups,
coiling or
of a polypeptide
between
R-groups
and the peptide
backbone
+pKCOOH), where pKi and pKj are the dissociation constants of the ionization
protein molecules
in a multi-subunit complex by
hydrogen
bond, electrostatic
attraction
and sulfide
Quaterna
groups involved.
bridge. Shape produced by combination of Bonds and other interactions between R-groups, and
ry
polypeptides
between
peptide
backbones
of
different
polypeptides
At its isoelectric point, amino acid remains stationary under an applied electric When functional unit consist of two or more structural domains, we speak of the quaternary
field.
structure of the protein.
Acid-Base Properties
It is the linear sequence of amino acids in a protein that determines the 3-dimensional folded
pH and pKa
structure of that protein.
The pH of a solution is a measure of the acidity of the solution. It is defined as
Another way to state this concept is to say that proteins fold to their thermodynamically
Where ] is the concentration of hydronium ions in the solution.
most stable state; ie, each particular folded protein has maximized all its particular
Consequently, the pH of a solution depends on two things
combinations of possible hydrogen bonds, electrostatic interactions, hydrophobic interactions, etc,
-The concentration of the solution if we have two solutions of the same acid, the in its final folded shape:
more concentrated solution will have more free H3O+ ions and therefore a lower
pH.
-The acid in question if we have two equally concentrated solution of acid, the
solution of a strong acid will have a lower pH than that of a weak acid, because it
is fully dissociated and therefore produces more H3O+ ions. HCL for example, is
completely dissociated.
Therefore, we see that pH does not measure the strength of an acid, but the
acidity of a given solution.
The pH of water is 7. This means that a solution of pure water has 10-7 mol/dm3 To demonstrated that the linear sequence of amino acids in a protein determines the folded
of hydronium ions. This can only happen through the autoprotolysis of water:
structure of that protein. Using a chemical called urea, he unfolded a protein called Ribonuclease-A,
and then reduced its internal disulfide bonds with mercaptoethanol. (Disulfide bonds stabilize the
This mean that in water,
folded protein in its original shape.) When the urea and mercaptoethanol is removed, the
To be clearer about what a strong and weak acid is, we look at the reaction:
ribonuclease renatured back, and regained full enzymatic activity. Based on experiments, the
information for the complete, correct folding of a protein is in the linear AA sequence of that protein.
The position of the equilibrium is measured by the equilibrium constant
One of the impt functions of proteins is to serve as catalysts for chemical reactions necessary for
Now, in dilute solutions of acid, stays roughly constant at about 56 mol/dm3. we life. Proteins that functions as chemical catalysts are called enzymes. The complex surface of a