Biochemistry
Topic 1: Chemical nature of enzymes, general properties of proteins:
Proteins:
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The biochemically smallest functional subunit is an amino acid. This is the primary structure.
The secondary structure is formed by many several amino acids connected with peptide
bonds. The tertiary structure is the 3D structure of the protein. Only in proteins which consist
of 2 or more polypeptide chains there is a quaternary structure.
Proteins have an amino acid skeleton. The amino acids themselves have a constant skeleton
(NH2-CH-COOH) and a variable side chain, which varies in shape, charge and hydrophobicity.
With the exception of Glycine (NH2-CH2-COOH) all amino acid have a chiralic center and will
be in L configuration.
Secondary Structures:
Name
Shape
Extra Information, Examples
Picture
α-helix
Coil like
structure
3.6 amino acids per turn,
Hydrogen bonds at iNH and
i+4CO
β-sheet
Form sheets
Can be parallel (left side of
picture) or antiparallel (right
side of picture)
β-turn
Form a
turnaround /
corner
Are stabilized by a hydrogen
bond
β-barrel
β-proppelers
Parallelhelical β
structures
α/β
structures:
TIM Barrel
Rossman
folds
Horseshoe
fold
Superoxide dismutase, porin
Noraminidase
Coil-like
Open barrel
Triose phosphate isomerase
Lactate dehydrogenase
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The tertiary structure will be a 3 dimensional structure which will be the most stable
structure (ΔGF < ΔGD). The 3D structure depends on the primary structure and if there has
ben an error during translation or transcribtion or there has been a DNA mutatuin the most
stable 3d structure might not be achieved this might result in a less or even inactive protein.
Hydrophobic amino acids will be in the core of the protein, hydrophilic will be presented on
the outside to achive the most stable conformation. This conformation will be affected by
attractive and repulsive forces :
Attractive force:
Discribtion
Example
Covalent bond
Equal sharing of an electron Peptide and disulfide
pair by 2 atoms.
bonds, c-c
Coordinate covalent bond
Unequal sharing of an
Fe2+ in hemoglobin
electron pair by 2 atoms.
The electron pair comes
originally just from one
atom. Electronpair donor is
the ligand or lewis base and
the acceptor the central
atom or lewis acid.
Important in interactions
between Transition metals
and organic ligands
Ionic interactions
Electrostatic attraction
These bonds are formed
between 2 groups of
between positively charged
different charge.
(a-ammonium, eammonium, guanidinium,
and imidazolium) side
chains and negatively
charged (ionized forms of
ot-carboxyl, fl-carboxyl, ycarboxyl, phosphate, and
sulfate) groups.
Hydrogen bonds
Sharing of a hydrogen atom N-H (peptide nitrogen,
between two
imidazole, and indole),-SH
electronegative atoms that (cysteine),- OH (serine,
have unbounded electrons. threonine, tyrosine, and
hydroxyproline),- NH2 andNH~- (arginine, lysine, and
oe-amino), and-CONH2
(carbamino, asparagine,
and glutamine). Groups
capable of sharing a
hydrogen atom include COO- (aspartate,
glutamate, and otcarboxylate),-SCH3
(methionine),-S-S
(disulfide), and/~ C=O (in
peptide and ester linkages).
Van der Waals forces
A fixed dipole in one
Nonpolar interior structure
molecule that induces
of proteins.
rapidly oscillating dipoles in
Hydrophobic interactions
Repulsive Forces
Electrostatic repulsion
Van der Waals repulsive forces
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another molecule through
distortion of the electron
cloud. The positive end of a
fixed dipole will pull an
electron cloud toward it;
the negative end will push
it away. Strength depends
very much on the distance.
They cause nonpolar side
chains (aromatic rings and
hydrocarbon groups) to
cling together in polar
solvents, especially water.
These interactions do not
produce true "bonds," since
there is no sharing of
electrons between the
groups involved. The
groups are pushed together
by their "expulsion" from
the polar medium.
important in lipid-lipid
interactions in membranes
This occurs between
charged groups of the same
charge. It is the opposite of
ionic forces.
They operate between
atoms at very short
distances from each other
and result from the dipoles
induced by the mutual
repulsion of electron
clouds. Since there is no
involvement of a fixed
dipole (in contrast to van
der Waals attractive
forces), the dependence on
distance in this case is even
greater.
Membrane Proteins have a sequence of hydrophobic amino acids that will be inside the lipid
bilayer membrane as the phospholipids are hydrophobic. Some will cross the membrane
several times others only once. Cytosolic proteins are membrane proteins which do not cross
the membrane but are only attached to one side of the membrane.
Proteins can be separated according to their size, charge at a specific pH, MW, solubility or
affinity to other substances
Proteins have domains (parts with specific functions)
The isoelectric point - pI – is the pH at which the net charge of the protein equals zero. At this
point the Protein will loose all its “connections” with water molecules and sink to the
bottom.
Proteins can have additional groups or substances
o
o
o
o
o
o
Lipoproteins
Glicoproteins (Ig)
Phosphoproteins (Casein)
Hemoproteins (hemoglobin)
Flavoproteins (succinate dehydrogenase)
Methaloproteins (ferittin – Fe, Alcohol dehydrogenase – Zn, Calmodulin – Ca)
Enzymes:
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Enzymes are proteins. They catalyze chemical reactions within the body: E+S->ES->EP->E+P.
They can catalyze reactions in both ways and are very specific to the substrate they work on.
Sometimes the enzymes need some inorganic cofactors for their proper action: Fe2+ or Fe3+ In
peroxidase, K+ in pyruvate kinase, Mg2+ (in hexokinase, glucose-6-phosphatase, pyruvate
kinase), Mn2+ (ribonucleotide reductase), Ni2+ (urease), Zn2+ (carbonic anhydrase,
carboxypeptidase A and B)
MW of proteins can vary between 12kDa to 1000kDa and even more.
Terms:
Configuration: The absolute arrangement of atoms around an atom. This arrangement can not be
altered in any way without breaking a covalent bond (for example D and L chiral conformers)
Conformation: The relative arrangement of atoms around an atom. This arrangement can be altered
without breaking a bond (non chiral conformers can cahinge the relative position their atoms without
breaking a covalent bond)