| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | transloc_2 | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 0
(#^-1 s^-1) | 0
(s^-1) | Not applicable** | - | Substrate:
CaMKII-thr286*-C
aM
NMDAR
Products:
CaMKII-thr286-Ca
M-PSD
|
| Same as for transloc_1 | | 2 | transloc_1 | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 0
(#^-1 s^-1) | 0
(s^-1) | Not applicable** | - | Substrate:
CaMKII-CaM
NMDAR
Products:
CaMKII-CaM-PSD
|
| Rates to match curve in fig2 from Shen and Meyer, Science 284:162-166(1999), calculated for 6:1 alpha:beta CaMKII heterodimers | | 3 | Stoch_Basal_
CaMKII_PSD | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 1
(s^-1) | 1
(s^-1) | Keq = 1(uM) | 0.5sec | Substrate:
basal_CaMKII_
PSD_control
Products:
basal_CaMKII_
PSD
|
| 4 | Inact-PP1 | PP1
Pathway No. 260 | 499.981
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate:
I1*
PP1-active
Products:
PP1-I1*
|
| K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 | | 5 | Inact-PP1 | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 499.98
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0002(uM) | - | Substrate:
I1*
PP1-active_PSD
Products:
PP1-I1*
|
| K inhib = 1nM from Cohen Ann Rev Bioch 1989, 4 nM from Foukes et al Assume 2 nM. kf /kb = 8.333e-4 | | 6 | equilib | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 540
(s^-1) | 60
(s^-1) | Not applicable** | - | Substrate:
CaM-Ca4-PSD
Products:
CaM-Ca4
|
| Diffusional equilibrium between PSD- and cytosolic compartment. According to D. Bary in Cell Movements 2nd ed 2001 D for proteins is 5e-7 cm^2/s giving 10 ms for a translocation of 1 um. | | 7 | dissoc-PP1-I1 | PP1
Pathway No. 260 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
PP1-I1
Products:
PP1-active
I1
|
| Let us assume that the equil in this case is very far over to the right. This is probably safe. | | 8 | dissoc-PP1-I1 | PP1_PSD
Pathway No. 262 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
PP1-I1
Products:
I1
PP1-active_PSD
|
| Let us assume that the equil in this case is very far over to the right. This is probably safe. | | 9 | Ca_stoch_PSD | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_PSD
Products:
Ca-PSD
|
| 10 | Ca_stoch_cyt | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_cyt
Products:
Ca
|
| 11 | CaMKII-thr286-bi
nd-CaM-PSD | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 1000.02
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate:
CaMKII-thr286-PS
D
CaM-Ca4-PSD
Products:
CaMKII-thr286-Ca
M-PSD
|
| Same values as for the main compartment Can the main compartment pool of Ca/CaM be used? | | 12 | CaMKII-diss-CaM | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 5
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate:
CaMKII-CaM-PSD
Products:
CaM-Ca4-PSD
CaMKII-PSD
|
| 13 | CaMKII-bind-CaM-
PSD | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 49.9998
(uM^-1 s^-1) | 0
(s^-1) | - | - | Substrate:
CaMKII-PSD
CaM-Ca4-PSD
Products:
CaMKII-CaM-PSD
|
| 14 | CaMKII-bind-CaM | CaMKII
Pathway No. 258 | 49.9997
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.1(uM) | - | Substrate:
CaM-Ca4
CaMKII
Products:
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. 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. | | 15 | CaMK-thr286-bind
-CaM | CaMKII
Pathway No. 258 | 1000.19
(uM^-1 s^-1) | 0.1
(s^-1) | Kd(bf) = 0.0001(uM) | - | Substrate:
CaMKII-thr286
CaM-Ca4
Products:
CaMKII-thr286*-C
aM
|
| 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 | | 16 | CaMCa4-bind-CaNA
B | PP2B
Pathway No. 261 | 599.994
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0017(uM) | - | Substrate:
CaM-Ca4
CaNAB-Ca4
Products:
CaM_Ca_n-CaNAB
|
| 17 | CaM-TR2-Ca2-bind
-Ca-PSD | CaM
Pathway No. 259 | 3.6
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate:
CaM-TR2-Ca2-PSD
Ca-PSD
Products:
CaM-Ca3-PSD
|
| K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10 | | 18 | CaM-TR2-Ca2-bind
-Ca | CaM
Pathway No. 259 | 3.6
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 2.7778(uM) | - | Substrate:
CaM-TR2-Ca2
Ca
Products:
CaM-Ca3
|
| K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10 | | 19 | CaM-TR2-bind-Ca-
PSD | CaM
Pathway No. 259 | 72
(uM^-2 s^-1) | 72
(s^-1) | Kd(af) = 1(uM) | - | Substrate:
CaM-PSD
Ca-PSD
Ca-PSD
Products:
CaM-TR2-Ca2-PSD
|
| Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !).... | | 20 | CaM-TR2-bind-Ca | CaM
Pathway No. 259 | 71.999
(uM^-2 s^-1) | 72
(s^-1) | Kd(af) = 1(uM) | - | Substrate:
CaM
Ca
Ca
Products:
CaM-TR2-Ca2
|
| Lets use the fast rate consts here. Since the rates are so different, I am not sure whether the order is relevant. These correspond to the TR2C fragment. We use the Martin et al rates here, plus the Drabicowski binding consts. All are scaled by 3X to cell temp. kf = 2e-10 kb = 72 Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11. If kb=72, kf = 2e-10 (Exactly the same !).... |
and 
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