FIGURE 5.

Simulation of K and V type regulation of αCaMKII. A, Equation 1 was used with K_m4 and V_max values for wild type CaM (solid line) and CaM3 (dotted and dashed line) mutant (Table 1), with [ATP] at 1 mm. The previously determined value of 80 nm was used for K_d3, the dissociation constant for Ca²⁺_n·CaM binding to αCaMKII·ATP (22). The dotted line represents data at 6 μm CaM3, and the dashed line represents data at 0.1 μm CaM3. K type switch is indicated by the substantial left shift of the activation curve by increasing the Ca²⁺·CaM concentration and by occupancy of EF-hand 3 in the CaM C lobe. B, Equation 2 was used with parameters V_max, K_act1, n, and K_m4 values for wild type CaM (solid line) and CaM1 mutant (dotted line), as shown in Table 1, with [ATP] at 1 mm. The V type activity switch is demonstrated by the large jump in activity by occupancy of the N lobe EF-hand 1. Equation 1, v = k_cat [αCaMKII]_o/(1 + K_m4/[ATP] +K_d3/[Ca²⁺_n·CaM] + K_d3K_m4/[ATP][Ca²⁺_n·CaM]), where n is the measured Hill coefficient. Equation 2, v = k_cat [αCaMKII]_o/(1 + K_m4/[ATP] + K_act1ⁿ/[Ca²⁺]ⁿ + K_act1ⁿK_m4/[Ca²⁺]ⁿ[ATP]), where n is the measured Hill coefficient.