What they found
Masada et al. used GST pull-down, mass spectrometry, and stopped-flow fluorescence to dissect how calmodulin (CaM) binds and activates adenylyl cyclase 1 (AC1) vs AC8. Key finding: AC1 is activated by an initial encounter complex between CaM and the IQ-like domain in the N-terminus, forming a 1:1 AC1:CaM complex at physiological Ca²⁺ concentrations. Activation is cooperative with Ca²⁺ occupancy of CaM’s C-lobe driving the stimulatory interaction. This establishes the mechanistic basis for AC1’s Ca²⁺/CaM sensitivity.
Numbers that matter
- AC1 activation by Ca²⁺/CaM: cooperative, driven by C-lobe Ca²⁺ binding
- Calmodulin binding stoichiometry: 1:1 (AC1:CaM)
- Mechanism: IQ-like domain in AC1 N-terminus is the primary CaM docking site
- AC8 uses a different (IQ-motif independent) mechanism — not applicable to h05
- K_Ca for AC1 activation not given as a single Kd number — determined by CaM affinity constants (~nM–µM range depending on Ca²⁺ saturation state)
- Note: the model’s
K_CA_AC1_NM = 150 nMandAC1_VMAX_NM_S = 2000 nM/sare not directly tabulated here; these likely derive from earlier biochemical work (Willoughby & Cooper 2007 review synthesis).
Fit to h05
This is the AC1 kinetics reference for the pivot model. The “Wu 2011” citation in the scripts is a phantom — Masada 2012 is the real paper. However, Masada 2012 gives mechanistic insight and relative rates, not the exact nM/s Vmax values used in the ODE. Those values require supplemental justification from Willoughby & Cooper 2007 or explicit labeling as estimates.
Connections
- STRC Calcium Oscillation Acoustic Therapy — AC1 kinetics underpins pivot model
[see-also]2007-willoughby-cooper-adenylyl-cyclase-review — companion canonical review[part-of]calcium-oscillation (literature-params topic)