Intersubunit communication

The salient features of this model involve the binding of the /3 subunit ligand serine and its activation through a PLP-dependent reaction to form a reactive enzyme-bound aminoacrylate (PLP AA) species that in turn triggers a conformational change that promotes the cleavage of IGP to indole at the a subunit. When a molecule of indole is formed it diffuses rapidly through the hydrophobic tunnel to the (3 subunit and reacts with the PLP AA, also very rapidly, to form the product tryptophan. This intersubunit communication keeps the a and /3 reactions in phase such that the intermediate indole does not accumulate. 

The model for a—j3 intersubunit communication indicates that it is the formation of the aminoacrylate species that leads to activation of the a reaction. When both serine and IGP are added simultaneously to the enzyme in a single enzyme turnover experiment, there is a lag in the cleavage of IGP that is a function of the reaction of serine to form the aminoacrylate species. Accordingly, amino acids other than serine that can undergo dehydration to form the aminoacrylate such as cysteine should serve as alternate substrates but should lead to a longer lag for the a subunit activation as determined by transient kinetic analysis. Cysteine does... 

Eaton, W. A. (1992). Speed of intersubunit communication in proteins. Biochemistry, 31,6692-702. 

On the basis of a consensus reached with the CAPRI community, a total of eight parameters are evaluated. " Two assess residue-residue contacts between the docked proteins. f nat is the fraction of intersubunit residue-residue contacts present in the X-ray structure of the target that are reproduced (recalled) in the model (residues are deemed in contact if any of their atoms are within 5 A) f non-nat is the fraction of residue contacts in... 

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