| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | 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
|
| 2 | 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
|
| 3 | 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 !).... | | 4 | 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 !).... | | 5 | 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. | | 6 | 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 | | 7 | 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 | | 8 | CaM-Ca3-bind-Ca-
PSD | CaM
Pathway No. 259 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5048(uM) | - | Substrate:
CaM-Ca3-PSD
Ca-PSD
Products:
CaM-Ca4-PSD
|
| Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 | | 9 | CaM-Ca3-bind-Ca | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 0.465
(uM^-1 s^-1) | 10
(s^-1) | Kd(bf) = 21.5054(uM) | - | Substrate:
CaM-Ca3
Ca
Products:
CaM-Ca4
|
| Use K3 = 21.5 uM here from Stemmer and Klee table 3. kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10 | | 10 | 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. | | 11 | Ca-bind-CaNAB-Ca
2 | PP2B
Pathway No. 261 | 3.6001
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.527(uM) | - | Substrate:
Ca
Ca
CaNAB-Ca2
Products:
CaNAB-Ca4
|
| This process is probably much more complicated and involves CaM. However, as I can't find detailed info I am bundling this into a single step. Based on Steemer and Klee pg 6863, the Kact is 0.5 uM. kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11 | | 12 | Ca-bind-CaNAB | PP2B
Pathway No. 261 | 10008
(uM^-2 s^-1) | 1
(s^-1) | Kd(af) = 0.01(uM) | - | Substrate:
CaNAB
Ca
Ca
Products:
CaNAB-Ca2
|
| going on the experience with CaM, we put the fast (high affinity) sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM. Assuming 10 nM at first, we get kf = 2.78e-8, kb = 1. Try 20 nM. kf = 7e-9, kb = 1 | | 13 | 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
|
| 14 | 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
|
| 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 | 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 | | 17 | 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? | | 18 | 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 | | 19 | back_1 | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 0.3
(s^-1) | 0
(#^-1 s^-1) | Not applicable** | - | Substrate:
CaMKII-PSD
Products:
CaMKII
NMDAR
|
| Rates set by the translocation experiments of Shen and Meyer, Science 1999. | | 20 | back_2 | Shared_Object_
CaMKII_noPKA_
model3
Pathway No. 257 | 0.3
(s^-1) | 0
(#^-1 s^-1) | Not applicable** | - | Substrate:
CaMKII-thr305-PS
D
Products:
CaMK-thr305
NMDAR
|
| Same as for back_1 |
** This is a trasport reation between compartments of different volumes. Therefore Kd is not applicable. Please Note Kf, Kb units are in number of molecules instead of concentration
and 
color.
