Transcript Relationship between the structure and function of proteins

Relationship between the structure
and function of proteins
Myoglobin
Myoglobin
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It is located in the muscle tissue and is responsible for its brown
color.
Its function is to store and transport oxygen in the skeletal muscles.
It is a relatively small protein made up of a single polypeptide chain
that contains 153 amino acid residues .
It contains a heme group (which is a prosthetic group consisting of a
protoporphyrin organic ring and a central iron atom).
It is the heme group which is responsible for the oxygen binding
capacity of Myoglobin.
Myoglobin is very similar to Hemoglobin in both its function and
structure ( since both are capable of oxygenation and
deoxygenation).
Myoglobin is an extremely compact molecule(in its interior there is
room for only 4 H2O molecules)
The backbone of the polypeptide chain is made up of 8 segments of
α-helical structures , the largest segment has 23 a.a while the
shortest 7 a.a residues .
• Thus 70% of the main polypeptide chain in myoglobin
is involved in α-helical structures.
• The rest of the polypeptide chain is loops or bends
between the α-helical segments.
• The non-polar amino acids are arranged in the interior
(e.g Leu, Val, Phe)thus producing a hydrophobic
interior.
• The polar or charged amino acids( e.g Glu, Asp , ) are
located on the outer surface , except for 2 His
residues which are in the interior since they play a
critical role in binding iron.
Binding of the heme group
• The heme group of myoglobin sits in a cleft in
the interior of the molecule lined with nonpolar a.a (except for the 2 His).
• There are 2 His in the interior of the
myoglobin molecule , the proximal His which
binds directly to the iron atom , the second
His does not interact directly with the heme
group , but helps stabilize the binding of the
O2 to the ferrous atom.
Binding of the heme group
Hemoglobin
Hemoglobin
• Hemoglobin is an oligomeric protein which is
composed of 4 polypeptide chains .
• Each poypeptide chain has a heme prosthetic
group attached to it in which the iron atom is
in the fe2+ state .
• The protein part of hemoglobin is called
globin which consists of 2 α chains (141 amino
acid residue) and 2β chains (146 amino acid
residues).
• It is roughly spherical with a 5.5 nm diameter.
• The single polypeptide chain (subunit) resembles
in its structure the structure of myoglobin , thus
the α and β chains contain several segments of αhelix separated by bends.
• Each heme is partially burried in a hydrophobic
pocket lined with non-polar amino acids.
• The heme group is bound to its poypeptide chain
through a coordination bond of the iron atom to
the R- group of the proximal His residue.
The Heme
• It consists of a complex organic ring structure
(protoporphyrin) which is a tetrapyrrol ring linked by four
methene bridges ( =CH groups) .
• It contains methyl , vinyl ,propionic acid groups attached to
the pyrrol rings.
• The non-polar vinyl group is burried in the hydrophobic
interior while the hydrophilic groups of the propionic acid
projects out of the pocket to the outside.
• The iron atom has 6 coordination bonds .
• Four in the plane of the portophyrin ring and attached to it
by binding to the 4 central nitrogen atoms , the two
remaining coordination bonds are perpendicular to the
heme plane where one will bind to nitrogen atom of the
proximal His residue and the other will bind the O2
molecule.
Structure of the heme group
Hemoglobin
Hemoglobin undergoes conformational changes on
binding oxygen;
The Hemoglobin molecule can presume two major
conformations, the R-state (relaxed state) , and the Tstate (tensed state).
Although Oxygen can bind to both conformations but it
shows a significantly higher affinity towards the Rstate.
The T-state is stabilized by a number of ionic bonds
between the (α1β1 ) and (α2β2 ) dimers.
The binding of oxygen to a hemoglobin subunit in the Tstate triggers a conformational change to the favored
R-state , through the breaking of some of the ionic
bonds with the formation of some new ones.
• By changing its conformation, hemoglobin is able
to bind and release oxygen molecules.
• The T → R conformational transition of
hemoglobin, involving its quaternary structure is
strictly related to the cooperative behaviour of
this protein in its reaction with oxygen.
• The configuration of low affinity, deoxygenated
hemoglobin (Hb) is known as the tense (T) state.
Conversely, the configuration of the fully
oxygenated high affinity form of hemoglobin
(HbO2) is known as the relaxed (R) state.
Spectral properties of HB
• When there is no oxygen bound to the HEME,
Hb absorbs at 430 nm, this is referred to as
DeoxyHemoglobin (DeoxyHb).
• When DeoxyHb bind to Oxygen, Hb absorbs
at 415 nm, this is referred to as
OxyHemoglobin (OxyHb).
• The fractional O2 saturation Y can be
calculated from this data
Binding of oxygen to myoglobin
and hemoglobin
Hemoglobin
The Bohr Effect;
• The effect of pH on the O2 - Hb equilibrium is called
the Bohr effect ;
• HHb + O2
HbO2 + H+ .
• When Hb is oxygenated it ionizes to free one H+ for
each O2 bound as seen in the equation.
• Since the reaction is a reversible reaction , increasing
the [ H+ ] will cause the equilibrium to shift to the left
releasing the O2 .
• The relationship between pH and the Hb %Oxygen
saturation is directly related .
Hemoglobin
• This pH effect and the sigmoidal property of Hb allows
it to carry O2 Efficiently .
• In the lungs where the partial pressure of O2 is high
approximately 100 mm Hg , and the pH is also high
7.4 ,the environment favors the binding of O2 .
• Whereas at the tissues where the pO2 is lower and the
pH is lower deoxygenation of Hb is favored.