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Molecule Parameter List for CaM-Ca4 | The statistics table lists the distribution of a molecule acting either as a substrate, product, enzyme or as a molecule within the network.
The text color of a molecule is highlighted by  color. | | Statistics |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | Synaptic_
Network | 16 | Network |
Shared_Object_Synaptic_Network, PKC, PLA2,
PLCbeta, Gq, MAPK,
Ras, EGFR, Sos,
PLC_g, CaMKII, CaM,
PP1, PP2B, PKA,
AC, CaRegulation | This model is an annotated version of the synaptic signaling network.
The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated.
Bhalla US Biophys J. 2002 Aug;83(2):740-52
Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62 |
CaM-Ca4 acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | CaM-Ca4 | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 0 | 1000 | No | | The four-calcium-bound form of CaM. It is the active form for most reactions. |
CaM-Ca4 acting as a Substrate in a reaction in Synaptic_Network Network
| 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 reaction are not consider. |
| | Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | 1 | CaM-bind-GEF | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 60
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate
CaM-Ca4
inact-GEF
Product
CaM-GEF
| | | We have no numbers for this. It is probably between the two extremes represented by the CaMKII phosph states, and I have used guesses based on this. kf=1e-4 kb=1 The reaction is based on Farnsworth et al Nature 376 524-527 1995 | | 2 | CaMKII-bind-CaM | Synaptic_
Network
Accession No. : 16 | CaMKII
Pathway No. : 80 | 49.9998
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.1(uM) | - | Substrate
CaM-Ca4
CaMKII
Product
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. | | 3 | CaMK-thr286-bind
-CaM | Synaptic_
Network
Accession No. : 16 | CaMKII
Pathway No. : 80 | 1000.2
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate
CaM-Ca4
CaMKII-thr286
Product
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. | | 4 | CaMCa4-bind-CaNA
B | Synaptic_
Network
Accession No. : 16 | PP2B
Pathway No. : 83 | 600
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0017(uM) | - | Substrate
CaM-Ca4
CaNAB-Ca4
Product
CaMCa4-CaNAB
| | | This step is the starting point for calculating all the CaM-binding steps to CaNAB-Ca4. The calculation goes like this: From Stemmer and Klee 1994 Biochem 33 6859-6866 we have rates for Ca binding to CaM.Ca4.CaN. From detailed balance (Kd must be 1 around a loop) we can set ratios of Kds for CaMCa3 binding to CaN, and CaM-Ca2 binding to CaN. Thus those rates can come once we know the Kd for the current reaction of CaMCa4 binding to CaN. We'll ignore the Ca binding steps to CaM.Ca4.CaN since the reactions around the remaining part of the loop will settle pretty fast to the same levels. Finally, we estimate the kf=0.001 here from a series of simulations matching the curves in Stemmer and Klee. | | 5 | CaM-bind-AC1 | Synaptic_
Network
Accession No. : 16 | AC
Pathway No. : 85 | 49.9998
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.02(uM) | - | Substrate
AC1
CaM-Ca4
Product
AC1-CaM
| | | Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991 Assume a rapid CaM binding of 1/sec. | | 6 | CaM_bind_PDE1 | Synaptic_
Network
Accession No. : 16 | AC
Pathway No. : 85 | 720
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.0069(uM) | - | Substrate
CaM-Ca4
PDE1
Product
CaM.PDE1
| | | Borisy et al J Neurosci 12(3):915-923 For olf epithelium PDE1, affinity is 7 nM CaM and about 2 uM Ca which is consistent with it binding Ca4.CaM at 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. |
CaM-Ca4 acting as a Product in a reaction in Synaptic_Network Network
| 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 reaction are not consider. |
| Name | Accession Name | Pathway Name | Kf | Kb | Kd | tau | Reagents | | CaM-Ca3-bind-Ca | Synaptic_
Network
Accession No. : 16 | CaM
Pathway No. : 81 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5054(uM) | - | Substrate
Ca
CaM-Ca3
Product
CaM-Ca4
| | Use K3 = 21.5 uM here from Stemmer and Klee table 3. Stemmer and Klee 1994 Biochem 33:6859-6866 kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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