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Team 2
Cristina Morales
Mariana Elizondo
Christian Boada
Species
Interactions
A3BS
3AB
A2B2S2
AB3S3
B4S4
6BB
ANTICOOPERATIVITY
The binding of the first ligand molecules
to an oligomeric protein decreases the
apparent affinity for the other ligand sites.
Example:
glyceraldehyde 3-phosphate dehydrogenase.
Half-site reactivity: The binding of the first ligand induces a structural modification
of the protein which confers a practically infinite dissociation constant to the residual
sites.
Flip-flop mechanism: Each protomer of the dimeric enzyme is alternately
phosphorylated by the substrate, while the other protomer is dephosphorylated -> E. coli alkaline phosphate.
Every difference in ligand affinity for the proteins two states, corresponds an equal difference
in the subunit interaction energy of the free and ligand associated form.
KINETIC COOPERATIVITY:
RICARD MODEL
Ricards approach (1989) attempts to describe the way in which variation of
subunits interactions can change the catalytic constant.
Protomer arrangement
contribution
Quaternary constraint
contribution
The theories developed on the basis of this formulation lie on three postulates:
In each catalytic transition state the quaternary constraints are relieved.
The minimum number of conformations is assumed (as in the MWC and
KNF bonding models).
The conformation of the ligand transition state complex is the same, or
energetically indistinguishable, for all transition states.
The three postulates take into account that maximum catalytic efficiency occurs
when the enzyme conformation is complementary to the transition state of the
reaction.
Conclusions:
Weak interaction between subunits can imply a kinetic cooperative
phenomenon, although the substrate saturation curve is not a sigmoid.
Strong interaction between subunits:
The substrate binding cooperativity is positive and the kinetic
cooperativity must be positive.
The substrate binding cooperativity is negative and the kinetic
cooperativity can be negative or positive.
In a strong interaction between subunits, a strong catalytic cooperativity can
generate a substrate saturation curve with no sigmoidal shape.
Sigmoidal curve
in cooperativity