Apparent inhibition constant

The pH dependence of HIV-1 protease has been assessed by measuring the apparent inhibition constant for a synthetic substrate analog (b). The data are consistent with the catalytic involvement of ionizable groups with pK values of 3.3 and 5.3. Maximal enzymatic activity occurs in the pH range between these two values. On the basis of the accumulated kinetic and structural data on HIV-1 protease, these pK values have been ascribed to the... 

Our inhibitor design strategy was based on the premise that structural modifications in the base of purine riboside that enhance purine base hydration without impairing the binding of the hydrated species to the ADA binding site would result in purine riboside (PR) analogues with high ADA inhibitory potency. Since the apparent inhibition constant (Kj (app)) is related to the hydration equilibrium constant (Keq) and the inhibitory constant for the hydrated molecule (Kj ) by... 

An inhibition of an Mg2+ ATPase on corn root plasma membrane was also observed. Kinetic data on aluminum inhibition present a competitive pattern, as demonstrated by the Lineweaver-Burk plot with an apparent inhibition constant (K,) of 40 pM [44]. These results were obtained at pH 6.6. The authors suggested that the inhibition may be a result of either the formation of an inefficient substrate (Al-ATP) or an interaction directly with the enzyme structure. 

Apparent inhibition constant against purified kinases. Inhibition of ligand-induced receptor autophosphorylation in the cell lines indicated. 

Figure 4.6 Apparent inhibition constant as a function of ATP-concentration relative to Km for competitive inhibition (solid line), pure noncompetitive inhibition (dashed line) and uncompetitive inhibition (dotted line). The inhibition constant is 5 nM for each mechanism.

Most mechanisms for slow binding inhibition involve one or two kinetic steps during association of the inhibitor with the enzyme.32 In the one step mechanism, a high affinity complex (E-I, apparent inhibition constant K ), is generated directly, without any detectable intermediates. In the two-step process, there is an initial complex (E-I, apparent inhibition constant K ), in equilibrium with uninhibited enzyme, followed by a subsequent tightening to give the final complex (E-I ) with an overall steady state apparent inhibition constant K. ... 

This time, Q acts as a noncompetitive inhibitor with respect to B at unsaturating A concentrations (from the primary plot). Saturation with A overcomes the inhibition (from the secondary plot). With a noncompetitive pattern in Fig. 6, one can define the apparent inhibition constants, Kis = KiQ(,i+KifJA) and = Ki( i+KA/A), making them useful for calculation of Kiq from the observed vdues. 

Figures 9 and 10 show the graphical presentation of Eqs. (9.64) and (9.65), the product inhibition by P. With a noncompetitive inhibition pattern in Fig. 9, one can define the apparent inhibition constants, Xa=Kif(i+B/Ktt) and K-,s=K vKffiJ iKipJCfiX and with a competitive inhibition pattern in Fig. 10, the apparent inhibition constant JTi = TipCi+iTiA/A), making them useful for calculation of iTip from observed values.

T3rpes of inhibition relative to Apparent inhibition constant ... 

Calculated from the equation = I)SJ(S - So), where Kow is the apparent inhibition constant, / is the concentration of inhibitor. So is the slope of the uninhibited line from the competitive inhibition plot, and St is the slope of the inhibited line on the same graph for a particular (/). 

Synthetic benzophenones as 2,2 ,4,4 -tetrahydro-benzophenone, 3,4,5,2 ,3 ,4 -hexahydrobenzophe-none and 4,4 -dihydrobenzophenone displayed their inhibitory effects on xanthine oxidase with an order of activity of IC50 = 47.59,69.40 and 82.94 (JiM, respectively (Sheu et al. 2000). The apparent inhibition constant of 3,4,5,2 ,3 ,4 -hexahydrobenzophe-... 

According to this model, variation with pH of the apparent inhibition constant Ki PP is determined by the pK s of the free enzyme and of the enzyme-inhibitor complex. Therefore, computed pK s can be used to predict the pH dependence of the inhibition constant, whereupon they can be compared with experimental results. Regarding the experimental counterpart from the customary equation for reaction velocity in the presence of a competitive inhibitor,it can be shown, as described by Trylska et al., that... 

Another way to validate computed values is to consider the pH dependence of the apparent inhibition constant According to the kinetic model presented earlier, the variation of the apparent inhibition constant with pH is determined by the pK s of the free enzyme and of the enzyme-inhibitor complex. Substitution of the computed values into Eq. [66] indicates that the apparent inhibition constant should decrease significantly, at least by an order of magnitude, when the pH is changed from 5.5 to 7.0. However, measurements made with a cyclic urea inhibitor analog indicated no change in the value of the apparent inhibition constant in this pH range. 

They were also more potent than the D1-D2 conjugates by a factor of more than ten (Fig. 5a and Table 1) this may be due to steric blocking of the conjugated peptide moiety by the D1-D2 moiety. The apparent inhibition constant (iCj) of the peptide conjugate PK15 (Fig. lb) was calculated to be 1.5 nM using a previously described equation. ... 

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