Proteins

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Macromolecular Structure
Proteins They are a relatively homogeneous class
of molecules. All are the same type of linear
polymer built of various combinations of the same
20 amino acids differing only in the sequence.
Their functional diversity lies in the
three-dimensional structures that these linear
polymers can make by simply being linked in
different sequences.
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What do proteins do? Pretty much
everything Store and transport a variety of
molecules Guide flow of electrons in processes
such as photosynthesis Transmit information
between specific cells within an organ Control
passage of molecules across membranes of
compartmentalized cells and organelles Function
in immune system to defend against intruders
(antibodies) Control gene expression by binding
to specific sequences of nucleic acids to turn
them on/off Structural stability within cells
including hair, nails, tendons, and bones of
animals
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19 Amino Acids have this structure
Exception Proline
Only the R-group changes Always the L-isomer
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In proteins, the amino acid is linked together by
PEPTIDE BONDS
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Each amino acid in a polypeptide chain is
referred to as a residue Usually between 50 to
3000 linked together to form a polypeptide
chain gt 50 protein lt50 polypeptide This
polymeric, linear linkagePrimary sequence
structure The sequence of amino acids in a
protein/polypeptide chain generally identifies a
protein unambiguously.
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Peptide bond appears to have 40 double bond
character which makes it strong Rotation about
this bond is restricted and pretty planar
Trans- Conformer

Asymmetric center
Shorter bonds are stronger and have less movement.
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Cis- Conformer This conformation is not very
well liked except with proline. Cis-
conformations tend to create steric hindrance
and repulsions with the side chains of the amino
acids (R groups). All about energy.

Trans is favored energetically (fewer
repulsions). However, if the residue that
follows a peptide bond is a proline, its cyclic
side chain diminishes the repulsive effects and
Cis trans isomers are approximately the same
energetically (maybe around a factor of 4
difference rather than 1000). This could cause
problems from a structural analysis viewpoint
example D9K.
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Resonance of the peptide bond tend to
redistribute its electrons, and the polypeptide
backbone is correspondingly polar. The H and N
atoms appear, respectively, to have positive and
negative charges of 0.20 electrons, whereas C and
O, respectively, have positive and negative
charges of 0.42 electron. The positive and
negative charges help to give the protein its
functionality. This gives the peptide bond a
permanent dipole moment of 3.5 Debye units. The
peptide backbone of each residue contains one
potent hydrogen bond donor, -NH-, and a hydrogen
bond acceptor, -CO- this is critical for the 3-D
architecture of proteins.
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The peptide backbone is not very reactive
chemically. The only groups usually ionized are
the terminal a -amino and carboxyl groups, which
normally have pKa values of about 7.4 to 3.9,
respectively depending on the nature of the
terminal amino acid residue. A proton is added
or lost to internal peptide bonds only at
extremes of pH. The apparent pK value of the
amide NH for deprotonation is between 15 and 18
and is in the region of -8 to -12 for
protonation. The oxygen atom of the carbonyl
group is protonated more readily, with an
apparent pK of about -1. These properties
facilitate the exchange of hydrogen isotopes
between the backbone and aqueous solvents, which
is important to the study of protein fluctuations
in solution. The amide proton has the ability to
exchange with the solution to create a constant
exchange process.
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Glycine
It has no aC asymmetry Glycine is a very
flexible residue because there is no steric
hindrance. This allows glycine to be dynamic
. It is very common in loops.
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Aliphatics
Hydrophobic- They hate water but love each
other They also like other non-polar atoms.
They are referred to as STICKY. They help
stabilize the folded conformations of proteins.
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Cyclic imino residue
Rigid about the N- aC bond Slightly puckered
with gamma-Carbon raised a little If no amide
proton, can not hydrogen bond The peptide bond
before a proline likes to be cis.
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Hydroxyl groups

The OH loves to Hydrogen bond can act as a
switch in catalysis
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Acidic residues
Even though they look similar, the are not close
functionally due to the extra CH2 on
Glutamine. The COO group clearly likes positive
charges which makes these good for metal ion
binding. Proteins do whatever necessary to
dispel charge such as binding to metals.
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Amide Residues
Neither is too reactive Have polar ends and are
H-bond acceptors and donors e.g. If an Asn and
Gly are next to each other, a kink could possibly
form due to deamidation (side chain and backbone
react)why Gly?
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Basic Residues
Interact with DNA (nucleic acids)
Normally ionized but if not , the side chain
becomes very reactive and a potent
nucleophile Good H-bond donor Tend to be
hydrophobic within chain and very non-hydrophobic
at end of chain
Has a very long side chain which likes to
interact with water in solution because end is
polar Searches for negative species, mostly on
surface of proteins
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Imidazole ring
Tertiary amine Good nucleophile (donates
electrons) In its non-ionized form, the nitrogen
with the hydrogen is an electrophile and donor
for H-bonding. The other nitrogen is a
nucleophile and acceptor for hydrogen bonding.
Very versatile side of the residue. The 2 Ns
within the ring are denoted d1 and e2. Two
tautomers can exist where either N can be
protonated. Predominantly it appears that the e2
is the protonated one. Metals?
e2
d1
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Aromatics
The largest and most fluorescent side-chain.
Occurs least frequently.
The ring can re-orient. Flip..switch
The OH group makes it quite reactive. Can
hydrogen bond.
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The aromatic residues are responsible for
ultraviolet and fluorescence properties of
proteins, also known as chromophores. The
spectral properties of the side chains are very
sensitive to local environmental changes and are
useful probes of structures.
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Sulfur containing residues
Very reactive The CH2 can ionize at mild
alkaline conditions.
Non-polar and unreactive. The sulfur can not be
protonated. Acts as a nucleophile a little.
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Disulfide bonds can form between two cysteine
residues in deprotonating conditions. The
cysteines will lose their Hs when in a pH above
7. To break the bond, decrease pH below 7.