| |
Reaction
Name | Pathway Name /
Pathway No. | Kf | Kb | Kd | tau | Reagents |
| 1 | Ca-bind-CaNAB | PP2B
Pathway No. 285 | 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 | | 2 | CaMK-thr286-bind
-CaM | CaMKII
Pathway No. 282 | 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 | | 3 | CaMKII-thr286-bi
nd-CaM-PSD | CaMKII_PSD
Pathway No. 292 | 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? | | 4 | CaM_bind_PDE1 | AC
Pathway No. 289 | 719.982
(uM^-1 s^-1) | 5
(s^-1) | Kd(bf) = 0.0069(uM) | - | Substrate:
PDE1
CaM-Ca4
Products:
CaM.PDE1
|
| For olf epi PDE1, affinity is 7 nM. Assume same for brain. Reaction should be pretty fast. Assume kb = 5/sec. Then kf = 5 / (0.007 * 6e5) = 1.2e-3 | | 5 | CaMCa4-bind-CaNA
B | PP2B
Pathway No. 285 | 599.994
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0017(uM) | - | Substrate:
CaM-Ca4
CaNAB-Ca4
Products:
CaM_Ca_n-CaNAB
|
| 6 | equilib | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 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 | Inact-PP1 | PP1
Pathway No. 284 | 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 | | 8 | Inact-PP1 | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 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 | | 9 | cAMP_diffusion | AC
Pathway No. 289 | 300
(s^-1) | 5.4
(s^-1) | Not applicable** | - | Substrate:
cAMP
Products:
cAMP_in_dend
|
| Represents diffusion, from a volume of 9e-20 to 5e-18. Assuming neck dimensions of 0.1 x 0.1 microns, this works out to a diffusion const of about 270 um^2/sec, which is pretty conservative. It is what cAMP does in frog cilia. | | 10 | Ca_stoch_cyt | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_cyt
Products:
Ca
|
| 11 | Ca_stoch_PSD | Shared_Object_
AMPAR_CaMKII_
weak_coupling
Pathway No. 281 | 100
(s^-1) | 100
(s^-1) | Keq = 1(uM) | 0.005sec | Substrate:
Ca_control_PSD
Products:
Ca-PSD
|
| 12 | cAMP-bind-site-A
1 | PKA
Pathway No. 288 | 75.0006
(uM^-1 s^-1) | 110
(s^-1) | Kd(bf) = 1.4667(uM) | - | Substrate:
R2C2-cAMP2
cAMP
Products:
R2C2-cAMP3
|
| 13 | cAMP-bind-site-A
2 | PKA
Pathway No. 288 | 75.0006
(uM^-1 s^-1) | 32.5
(s^-1) | Kd(bf) = 0.4333(uM) | - | Substrate:
cAMP
R2C2-cAMP3
Products:
R2C2-cAMP4
|
| 14 | CaM-TR2-bind-Ca-
PSD | CaM
Pathway No. 283 | 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 !).... | | 15 | CaM-TR2-bind-Ca | CaM
Pathway No. 283 | 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 !).... | | 16 | Release-C1 | PKA
Pathway No. 288 | 60
(s^-1) | 17.9998
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C2-cAMP4
Products:
PKA-active
R2C-cAMP4
|
| This has to be fast, as the activation of PKA by cAMP is also fast. kf was 10 | | 17 | Release-C2 | PKA
Pathway No. 288 | 60
(s^-1) | 17.9998
(uM^-1 s^-1) | Kd(cb) = 0.3(uM) | - | Substrate:
R2C-cAMP4
Products:
PKA-active
R2-cAMP4
|
| 18 | inhib-PKA | PKA
Pathway No. 288 | 59.9994
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.0167(uM) | - | Substrate:
PKA-active
PKA-inhibitor
Products:
inhibited-PKA
|
| This has to be set to zero for matching the expts in vitro. In vivo we need to consider the inhibition though. kf = 1e-5 kb = 1 | | 19 | cAMP-bind-site-B
1 | PKA
Pathway No. 288 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2
cAMP
Products:
R2C2-cAMP
|
| Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M for type II, 5.6e-8 M for type I. Take mean which comes to 2e-13 #/cell Smith et al PNAS USA 78:3 1591-1595 1981 have better data. First kf/kb=2.1e7/M = 3.5e-5 (#/cell). Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs suggesting time course of complete assoc is < 1 min. | | 20 | cAMP-bind-site-B
2 | PKA
Pathway No. 288 | 54
(uM^-1 s^-1) | 33
(s^-1) | Kd(bf) = 0.6111(uM) | - | Substrate:
R2C2-cAMP
cAMP
Products:
R2C2-cAMP2
|
| For now let us set this to the same Km (1e-7M) as site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2) = 2e-13:2.77e-12 Smith et al have better values. They say that this is cooperative, so the consts are now kf/kb =8.3e-4 |
and 
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