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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 | Synaptic_
Network | 16 | Network |
Shared_Object_Synaptic_Network, PKC, PLA2,
PLCbeta, Gq, MAPK,
Ras, EGFR, Sos,
PLC_g, CaMKII, CaM,
PP1, PP2B, PKA,
AC, CaRegulation | This model is an annotated version of the synaptic signaling network.
The primary reference is Bhalla US and Iyengar R. Science (1999) 283(5400):381-7 but several of the model pathways have been updated.
Bhalla US Biophys J. 2002 Aug;83(2):740-52
Bhalla US J Comput Neurosci. 2002 Jul-Aug;13(1):49-62 |
I1 acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | I1 | Synaptic_
Network
Accession No. : 16 | PP1
Pathway No. : 82 | 1.8 | 1000 | 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-competitive, so it just turns the enzyme off without interacting with the binding site. Cohen et al 1989 Ann rev Biochem 58:453-508 refer to results where concentration of the inhibitor 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 Synaptic_Network Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | PKA-active /
PKA-phosph-I1 | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 7.5 | 9 | 4 | explicit E-S complex | Substrate
I1
Product
I1*
| | Numbers 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 since Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on phosphokinase beta. |
I1 acting as a Product of an Enzyme in Synaptic_Network Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | CaM(Ca)n-CaNAB /
dephosph_inhib1 | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 4.97076 | 0.34 | 4 | explicit E-S complex | Substrate
I1*
Product
I1
| | | Assume the rates are the same when dephosphorylating I1 either when it is floating freely, or when it is bound to PP1 catalytic subunit. This is from Liu and Storm 1989 264(22):12800-12804 | | 2 | PP2A /
PP2A-dephosph-I1
| Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 7.82828 | 6 | 4.16667 | 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 58:453-508 I use a Km twice that for the preferred substrates of PP2A. | | 3 | CaNAB-Ca4 /
dephosph_
inhib1_noCaM
| Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 4.97076 | 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 enzyme reaction. These numbers are from Liu and Storm JBC 1989 264(22):12800-12804 They say that the CaM-free form of CaN operates at about the same Km of 5 uM, but at a much lower Vmax of 1 nmol/min/mg. Other estimates of activity without CaM suggest 10% activity, which is what I use here. |
I1 acting as a Product in a reaction in Synaptic_Network 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 | | dissoc-PP1-I1 | Synaptic_
Network
Accession No. : 16 | PP1
Pathway No. : 82 | 1
(s^-1) | 0
(uM^-1 s^-1) | - | - | Substrate
PP1-I1
Product
I1
PP1-active
| | Assumption is that the affinity of the unphosphorylated form of I1 for PP1 is extremely weak and that the reaction is essentially all the way forward. The tau is fast at 1 sec. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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