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Accession Type:
Network
NonOsc_Ca_
IP3metabolism
MIPP
CaMKII
 Molecule
 Enzyme
 Reaction
CaM
PKC
IP3-3K
CaRegulation
Gq
PLCbeta
134_dephos
145_dephos
IP4-system
IHP-system
1345_dephos

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Reaction List for pathway CaMKII (Pathway Number 106)

Kd is calculated only for second order reactions, like nA+nB <->nC or nA<->nC+nD, where n is number and A,B,C,D are molecules, where as for first order reactions Keq is calculated. Kd for higher order reactions is not considered.
  Name KfKbKdtauSubstrateProduct
1 basal-activitykf
(s^-1)
0
(s^-1)
--CaMKII
CaMKII-thr286
  This reaction represents one of the 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. Lisman et al propose that the levels of PP1 are very low in the postsynaptic density, and PP2A is excluded from the PSD, and this would lead to autophosphorylation at a sustained level.
2 CaMK-thr286-bind
-CaM
kf
(uM^-1 s^-1)
0.1
(s^-1)
Kd(bf) = 0.0001(uM)-CaMKII-thr286
CaM-Ca4
  • CaMKII-thr286*-C
    aM

  •   Affinity is up 1000X over the unphosphorylated CaMKII, which makes the Kd of 0.1 nM. See Hanson et al 1994 Neuron 12:943-956. Time to release is about 20 sec, so the kb is OK at 0.1/sec. as tested by a few runs.
    3 CaMKII-bind-CaMkf
    (uM^-1 s^-1)
    5
    (s^-1)
    Kd(bf) = 0.1(uM)-CaM-Ca4
    CaMKII
    CaMKII-CaM
      This is tricky. There is some cooperativity here arising from interactions between the subunits of the CAMKII holoenzyme. However, the stoichiometry is 1. Kd = 0.1 uM. Rate is fast (see Hanson et al Neuron 12 943-956 1994) Hanson and Schulman 1992 AnnRev Biochem 61:559-601 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high. Low Ca = 100 nM = physiol.


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