Protein Primary Structure and the Peptide Bond Flashcards
Steric interactions
- Also known as ‘excluded volume’ interactions
- Two atoms cannot occupy the same region of space
simultaneously - When two atoms are brought very close:
- electron clouds of atoms overlap
- Pauli exclusion principle begins to apply
- Steric interactions allow us to understand many
conformational properties of molecules (but not all
short-range repulsion has
-an exponential dependence on
interatomic distance:
-E (proportional) exp(-r)
(note that it’s only
important at very short
distances)
-similar thinking applies to the conformational behavior of
amino acids (and proteins)
The peptide bond reactions: (2)
Water goes on…
hydrolysis
Water comes off…
condensation
The formation of the peptide bond results…
in the liberation
of one water molecule per two amino acids condensed.
Hydrolysis is favored thermodynamically in…
aqueous media.
But, the rate constant for the hydrolysis reaction is small.
So the reaction is too slow to be accomplished in a living cell
without the aid of enzymes.
Stability and Formation of Peptide Bond:
The peptide bond is metastable.
- That is, the favored reaction at RT° in aqueous solution is
HYDROLYSIS of the peptide bond - But, the uncatalyzed reaction is exceedingly slow.
Catalysis can occur via acid or base.
Specific catalysis is provided by…
proteolytic enzymes
or proteases
The Peptide Bond is…
- Is usually found in the trans conformation
- Has partial (40%) double bond character
- Is about 0.133 nm long - shorter than a typical single
bond but longer than a double bond - Due to the double bond character, the six atoms of
the peptide bond group are always planar! - N partially positive; O partially negative
Geometry of Peptide Bond:
Linus Pauling proposed that a
peptide bond is most accurately represented as a hybrid of
two contributing structures
the hybrid of two contributing structures has…
considerable C-N double bond character
and rotation about the peptide bond is restricted
A resonance hybrid of two forms…
The delocalization of (pi) electron orbitals gives the
peptide bond a partial double bond character.
Resonance in the Peptide Bond
The peptide group is a rigid, planar structure due to the
resonance interactions which give the peptide bond an
~40% double-bond character.
X-ray studies by Pauling and Corey provided…
the structural
basis for our understanding of the peptide group.
The Planar Nature of the
Peptide Bond
Six atoms of the peptide group lie in a plane!
Two configurations are possible,
both planar:
Trans is the favored configuration particularly with
bulky R groups.
Cis configuration = RARE
Virtually all peptide bonds in proteins have
the trans configuration.
The Peptide Bond: So Far (4)
- -electron delocalization over O-C-N fragment
- Resonance stabilization yields planar structure
- Adjacent Ca
atoms are in trans conformation to
prevent steric hindrance - Hydrolysis is thermodynamically favoured
The thermodynamic instability of polypeptides requires a…
mechanism
other than a straight forward dehydration reaction for their synthesis in
the aqueous medium of the cell.
- Indeed, coupling to ATP hydrolysis is involved
Free amino acids are NOT…
used to make
polypeptides / proteins in cells
Aminoacyl-RNA’s are…
the high energy
intermediates used in biosynthesis of
polypeptides
The ribosome has enzymatic activity:
promoting
peptide bond formation
Polypeptides have ends…
or terminals.
- Amino
or “ N”
terminus - Peptide bond
- Carboxyl
or “ C ”
terminus
In 1902, Emil Fischer proposed that…
proteins are long
chains of amino acids joined by amide bonds to which
he gave the name peptide bonds
Peptide bond Definition:
the special name given to the amide bond
between the a-carboxyl group of one amino acid and
the a -amino group of another
Peptide / dipeptide Definition:
The product of a reaction in which an amide bond is formed between two
amino acids
-the case of two amino acids,
tripeptide for 3 AAs, tetrapeptide for 4, etc
AMINO ACID
RESIDUE
Definition:
The portion of the original amino
acid that remains in the peptide
OLIGOPEPTIDES Definition:
peptides with only a few AA residues
POLYPEPTIDES Definiton:
long chain peptides with many AA residues
The linear sequence of amino acids within a peptide is written
from N-C, either in 3- or 1- letter code.
peptide Definition :
the name given to a short polymer of amino acids
joined by peptide bonds; they are classified by the number
of amino acids in the chain
dipeptide Definition:
a molecule containing two amino acids joined
by a peptide bond
tripeptide Definition:
a molecule containing three amino acids joined
by peptide bonds
polypeptide Definition:
a macromolecule containing many amino
acids joined by peptide bonds
protein Definition:
a biological macromolecule of molecular weight
5000 g/mol of greater, consisting of one or more
polypeptide chains
Peptides have…
Short polymers of amino acids
* Each unit is called a residue
* 2 residues -dipeptide
* 3 residues -tripeptide
* 12-20 residues - oligopeptide
* many - polypeptide
Peptides are…
Polyampholites
Polypeptides contain…
ionizable functions:
amino and carboxy termini and sidechains
charge (pH) determines
Solubility, structure, function, etc
Isoelectric Point Definition:
pH at which net charge is 0.
- I.P. is determined by sequence
Proteins are not just…
polypeptides.
- They are polypeptides of defined sequence.
- Each protein has a defined order of amino acid
residues. - This sequence is referred to as the primary
structure of the protein.
Linear arrays of amino acids can make…
a huge number of molecules.
For 100 amino acid protein the number of possibilities are:
20^(100) = 1.27x10^(130)
The total number of atoms in the universe is estimated at
9x10^(78)
Enkephalins:
Leucine enkephalin
Tyr-Gly-Gly-Phe-Leu
= Y-G-G-F-L
Methionine enkephalin
Tyr-Gly-Gly-Phe-Met
= Y-G-G-F-M
