Inhibition of prolidase by phosphoenolpyruvate is biphasic. avoidance of endogenous-metabolite inactivation by cooperativity within an enzyme dimer

A previously reported potent competitive inhibition of the dimeric enzyme prolidase by phosphoenolpyruvate is in fact biphasic. At pH 7.1 the first (partially) inhibiting moiety binds with a Ki of 0.30 μM, but a second binds more weakly, Ki′ of 0.24 mM. An explanatory cooperative interaction between enzyme monomers is postulated, so as to avoid inactivation of prolidase by prevailing physiological concentrations of PEP.