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Molecule Parameter List for GTP-Ras | 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 |
GTP-Ras acting as a Molecule in Synaptic_Network Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GTP-Ras | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 0 | 1000 | No | | Only a very small fraction (7% unstim, 15% stim) of ras is GTP-bound. Gibbs et al JBC 265(33) 20437 |
GTP-Ras 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 | GAP /
GAP-inact-ras | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 1.0104 | 10 | 100 | explicit E-S complex | Substrate
GTP-Ras
Product
GDP-Ras
| | From Eccleston et al JBC 268(36)pp27012-19 get Kd < 2uM, kcat - 10/sec From Martin et al Cell 63 843-849 1990 get Kd ~ 250 nM, kcat = 20/min I will go with the Eccleston figures as there are good error bars (10%). The two sets of values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting) This is one of the rare cases where we have direct info on the k3 being rate-limiting. Hence the ratio I use for the k2:k3 rates is 100 rather than the usual 4. |
GTP-Ras 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 | GEF-Gprot-bg /
GEF-bg_act-ras | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP-Ras
Product
GTP-Ras
| | | Kinetics based on the activation of Gq by the receptor complex in the Gq model (in turn based on the Mahama and Linderman model) k1 = 2e-5, k2 = 1e-10, k3 = 10 (I do not know why they even bother with k2). Lets put k1 at 2e-6 to get a reasonable equilibrium More specific values from, eg.g: Orita et al JBC 268(34) 25542-25546 from rasGRF and smgGDS: k1=3.3e-7; k2 = 0.08, k3 = 0.02 | | 2 | GEF* /
GEF*-act-ras | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP-Ras
Product
GTP-Ras
| | | Kinetics from Orita et al JBC 268(34):25542-25546. Note that the Vmax is slow, but it does match the slow GTP hydrolysis rates. | | 3 | CaM-GEF /
CaM-GEF-act-ras | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP-Ras
Product
GTP-Ras
| | | Kinetics same as GEF-bg_act-ras | | 4 | Shc*.Sos.Grb2 /
Sos.Ras_GEF | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 0.505051 | 0.02 | 4 | explicit E-S complex | Substrate
GDP-Ras
Product
GTP-Ras
| | | Rates from Orita et al JBC 268(34):25542-25546 |
GTP-Ras acting as a Substrate 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 | | 1 | Ras-act-craf | Synaptic_
Network
Accession No. : 16 | Shared_Object_
Synaptic_
Network
Pathway No. : 70 | 24
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0208(uM) | - | Substrate
GTP-Ras
craf-1*
Product
Raf-GTP-Ras*
| | | Assume binding is fast and limited only by available Ras*. So kf = kb/[craf-1] If kb is 1/sec, then kf = 1/0.2 uM = 1/(0.2 * 6e5) = 8.3e-6 Later: Raise it by 10 X to about 1e-4, giving a Kf of 60 for Kb of 0.5 and a tau of approx 2 sec. Based on: Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414. Also see Koide et al 1993 PNAS USA 90(18):8683-8686 | | 2 | Ras-intrinsic-GT
Pase | Synaptic_
Network
Accession No. : 16 | Ras
Pathway No. : 76 | 0.0001
(s^-1) | 0
(s^-1) | - | - | Substrate
GTP-Ras
Product
GDP-Ras
| | | This is extremely slow (kf = 1e-4), but it is significant as so little GAP actually gets complexed with it that the total GTP turnover rises only by 2-3 X (see Gibbs et al, JBC 265(33) 20437-20422) and Eccleston et al JBC 268(36) 27012-27019 There is no back reaction as we assume this to be a regular irreversible Michaelis-Menten zeroth order hydrolysis. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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