|
Enter a Search String | | Special character and space not allowed in the query term.
Search string should be at least 2 characters long. |
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 | |
GTP-Ras acting as a Molecule in MAPK-bistability-fig1c Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | GTP-Ras | MAPK-bistability
-fig1c
Accession No. : 35 | Ras
Pathway No. : 184 | 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 MAPK-bistability-fig1c Network
Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | GAP /
GAP-inact-ras | MAPK-bistability
-fig1c
Accession No. : 35 | Ras
Pathway No. : 184 | 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 MAPK-bistability-fig1c Network
| | Enzyme Molecule /
Enzyme Activity | Accession Name | Pathway Name | Km (uM) | kcat (s^-1) | Ratio | Enzyme Type | Reagents | | 1 | Shc*.Sos.Grb2 /
Sos.Ras_GEF | MAPK-bistability
-fig1c
Accession No. : 35 | Shared_Object_
MAPK-bistability
-fig1c
Pathway No. : 179 | 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 | | 2 | GEF* /
GEF*-act-ras | MAPK-bistability
-fig1c
Accession No. : 35 | Ras
Pathway No. : 184 | 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. |
GTP-Ras acting as a Substrate in a reaction in MAPK-bistability-fig1c 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-intrinsic-GT
Pase | MAPK-bistability
-fig1c
Accession No. : 35 | Ras
Pathway No. : 184 | 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. | | 2 | Ras-act-craf | MAPK-bistability
-fig1c
Accession No. : 35 | Shared_Object_
MAPK-bistability
-fig1c
Pathway No. : 179 | 60
(uM^-1 s^-1) | 0.5
(s^-1) | Kd(bf) = 0.0083(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 | | 3 | Ras-act-unphosph
-raf | MAPK-bistability
-fig1c
Accession No. : 35 | Shared_Object_
MAPK-bistability
-fig1c
Pathway No. : 179 | 6
(uM^-1 s^-1) | 1
(s^-1) | Kd(bf) = 0.1667(uM) | - | Substrate
GTP-Ras
craf-1
Product
RGR
| | | Based on rates of Ras-act-craf which has Kf=60, Kb= 0.5. This reaction was introduced to account for the PKC-independent activation of MAPK. This reac should have less affinity but similar tau as compared to the Ras-cat-craf, since the phosphorylated Raf form has a greater effect on MAPK. |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
This Copyright is applied to ensure that the contents of this database remain freely available. Please see FAQ for details. |
|
