| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | CaM-TR2-bind-Ca | CaM
Pathway No. 246 | 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 !).... | | 2 | CaM-TR2-bind-Ca-
PSD | CaM
Pathway No. 246 | 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 !).... | | 3 | equilib | CaM
Pathway No. 246 | 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. | | 4 | CaM-TR2-Ca2-bind
-Ca | CaM
Pathway No. 246 | 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 | | 5 | CaM-TR2-Ca2-bind
-Ca-PSD | CaM
Pathway No. 246 | 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 | | 6 | CaM-Ca3-bind-Ca-
PSD | CaM
Pathway No. 246 | 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 | | 7 | CaM-Ca3-bind-Ca | CaM
Pathway No. 246 | 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 | | 8 | neurogranin-bind
-CaM | CaM
Pathway No. 246 | 0.3
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 3.3333(uM) | - | Substrate:
neurogranin
CaM
Products:
neurogranin-CaM
|
| Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987 | | 9 |
neurogranin-bind
-CaM_
PSD | CaM
Pathway No. 246 | 0.3
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 3.3333(uM) | - | Substrate:
neurogranin_PSD
CaM-PSD
Products:
neurogranin-CaM_
PSD
|
| Surprisingly, no direct info on rates from neurogranin at this time. These rates are based on GAP-43 binding studies. As GAP-43 and neurogranin share near identity in the CaM/PKC binding regions, and also similarity in phosph and dephosph rates, I am borrowing GAP-43 kinetic info. See Alexander et al JBC 262:13 6108-6113 1987 | | 10 | dephosph-neurogr
anin | CaM
Pathway No. 246 | 0.005
(s^-1) | 0
(s^-1) | - | - | Substrate:
neurogranin*
Products:
neurogranin
|
| This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC. | | 11 |
dephosph-neurogr
anin_
PSD | CaM
Pathway No. 246 | 0.005
(s^-1) | 0
(s^-1) | - | - | Substrate:
neurogranin*_
PSD
Products:
neurogranin_PSD
|
| This is put in to keep the basal levels of neurogranin* experimentally reasonable. From various papers, specially Ramakers et al JBC 270:23 1995 13892-13898, it looks like the basal level of phosph is between 20 and 40%. I est around 25 % The kf of 0.005 gives around this level at basal PKC activity levels of 0.1 uM active PKC. |
and 
color.
