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Molecule Parameter List for I1 | 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 | | CaMKII_model3 | 63 | Network |
Shared_Object_CaMKII_model3, CaMKII, CaM,
PP1, PP2B, PP1_PSD,
AC, PKA | | This is the complete model of CaMKII bistability, model 3. It exhibits bistability in CaMKII activation due to autophosphorylation at the PSD and local saturation of PP1. This version of model 3 includes PKA regulatory input. This has little effect on the deterministic calculations, but the PKA pathway introduces a lot of noise which causes a difference in stochastic runs. |
I1 acting as a Molecule in CaMKII_model3 Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | I1 | CaMKII_model3
Accession No. : 63 | PP1
Pathway No. : 266 | 1.8 | 0.09 | No | | I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM. | | I1 | CaMKII_model3
Accession No. : 63 | PP1_PSD
Pathway No. : 268 | 4 | 0.01 | No | | I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183). We treat it as non-compet, so it just turns the enz off without interacting with the binding site. Cohen et al ann rev bioch refer to results where conc is 1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM, we need >= 1.8 uM. |
I1 acting as a Substrate for an Enzyme in CaMKII_model3 Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PKA-active /
PKA-phosph-I1 | CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 7.50008 | 9 | 4 | explicit E-S complex | Substrate
I1
Product
I1*
| | | #s from Bramson et al CRC crit rev Biochem 15:2 93-124. They have a huge list of peptide substrates and I have chosen high-ish rates. These consts give too much PKA activity, so lower Vmax 1/3. Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast). Also lower Km 1/3 so k1 = 1e-5 Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta. | | 2 | PKA-active /
PKA-phosph-I1_
PSD
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 7.50008 | 9 | 4 | explicit E-S complex | Substrate
I1
Product
I1*
|
I1 acting as a Product of an Enzyme in CaMKII_model3 Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | PP2A /
PP2A-dephosph-I1
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 15.9999 | 2 | 4.1667 | explicit E-S complex | Substrate
I1*
Product
I1
| | | PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6 | | 2 | PP2A /
PP2A-dephosph-I1
_
PSD
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 15.9999 | 2 | 4.1667 | explicit E-S complex | Substrate
I1*
Product
I1
| | | PP2A does most of the dephosph of I1 at basal Ca levels. See the review by Cohen in Ann Rev Biochem 1989. For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6 | | 3 | CaNAB-Ca4 /
dephosph_
inhib1_noCaM
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 4.97079 | 0.034 | 4 | explicit E-S complex | Substrate
I1*
Product
I1
| | | The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034 | | 4 | CaNAB-Ca4 /
dephosph_
inhib1_noCaM_
PSD
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 4.97071 | 0.034 | 4 | explicit E-S complex | Substrate
I1*
Product
I1
| | | The rates here are so slow I do not know if we should even bother with this enz reacn. These numbers are from Liu and Storm. Other refs suggest that the Km stays the same but the Vmax goes to 10% of the CaM stim levels. Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013 New : k1=5.7e-8, k2=.136, k3=.034 | | 5 | CaM_Ca_n-CaNAB /
dephosph_inhib1 | CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 4.97079 | 0.34 | 4 | explicit E-S complex | Substrate
I1*
Product
I1
| | 6 | CaM_Ca_n-CaNAB /
dephosph_
inhib1_PSD
| CaMKII_model3
Accession No. : 63 | Shared_Object_
CaMKII_model3
Pathway No. : 263 | 4.97071 | 0.34 | 4 | explicit E-S complex | Substrate
I1*
Product
I1
|
I1 acting as a Product in a reaction in CaMKII_model3 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 | dissoc-PP1-I1 | CaMKII_model3
Accession No. : 63 | PP1
Pathway No. : 266 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate
PP1-I1
Product
I1
PP1-active
| | | Let us assume that the equil in this case is very far over to the right. This is probably safe. | | 2 | dissoc-PP1-I1 | CaMKII_model3
Accession No. : 63 | PP1_PSD
Pathway No. : 268 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate
PP1-I1
Product
I1
PP1-active_PSD
| | | Let us assume that the equil in this case is very far over to the right. This is probably safe. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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