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Reaction Name | Pathway Name / Pathway No. | Kf | Kb | Kd | tau | Reagents |
1 | CaMKII-bind-CaM | CaMKII
Pathway No. 216 | 49.9998 (uM^-1 s^-1) | 5 (s^-1) | Kd(bf) = 0.1(uM) | - | Substrate: CaM-Ca4 CaMKII
Products: CaMKII-CaM
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| This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994) so lets say kb = 10. This gives kf = 1.6667e-4 H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol. | 2 | CaMK-thr286-bind -CaM | CaMKII
Pathway No. 216 | 1000.2 (uM^-1 s^-1) | 0.1 (s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate: CaMKII-thr286 CaM-Ca4
Products: CaMKII-thr286*-C aM
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| Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1 This makes Kf around 1.6666e-3 | 3 | basal-activity | CaMKII
Pathway No. 216 | 0.003 (s^-1) | 0 (s^-1) | - | - | Substrate: CaMKII
Products: CaMKII-thr286
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| This reaction represents one of the big unknowns in CaMK-II biochemistry: what maintains the basal level of phosphorylation on thr 286 ? See Hanson and Schulman Ann Rev Biochem 1992 61:559-601, specially pg 580, for review. I have not been able to find any compelling mechanism in the literature, but fortunately the level of basal activity is well documented. |