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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

*GTP-Ras* participated as	Molecule	Sum total of	Enzyme	Substrate of an enzyme	Product of an enzyme	Substrate in Reaction	Product in Reaction
No. of occurrences	1	0	0	1	1	2	0

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
MAPK_MKP1_ oscillation	9	Network	Shared_Object_MAPK_MKP1_oscillation, PKC, MAPK, PLA2, Ras
This model relates to figure 5 in Bhalla US, Iyengar R. Chaos (2001) 11(1):221-226. It includes the model used for figures 2-4 and also has MKP-1 induction by MAPK activity in the synapse. PP2A is set to 0.16 uM and MKP synthesis is varied from 5x to 40 x basal to get a range of interesting behaviours.

GTP-Ras acting as a Molecule in MAPK_MKP1_oscillation Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GTP-Ras	MAPK_MKP1_ oscillation Accession No. : 9	Ras Pathway No. : 63	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_MKP1_oscillation Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
GAP / GAP-inact-ras	MAPK_MKP1_ oscillation Accession No. : 9	Ras Pathway No. : 63	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%). In general the values are reasonably close. k1 = 1.666e-3/sec, k2 = 1000/sec, k3 = 10/sec (note k3 is rate-limiting)

GTP-Ras acting as a Product of an Enzyme in MAPK_MKP1_oscillation Network

Enzyme Molecule / Enzyme Activity	Accession Name	Pathway Name	Km (uM)	kcat (s^-1)	Ratio	Enzyme Type	Reagents
GEF* / GEF*-act-ras	MAPK_MKP1_ oscillation Accession No. : 9	Ras Pathway No. : 63	0.505051	0.02	4	explicit E-S complex	Substrate GDP-Ras Product GTP-Ras
Kinetics same as GEF-bg-act-ras

GTP-Ras acting as a Substrate in a reaction in MAPK_MKP1_oscillation 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	MAPK_MKP1_ oscillation Accession No. : 9	Shared_Object_ MAPK_MKP1_ oscillation Pathway No. : 59	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 4e-5 From Hallberg et al JBC 269:6 3913-3916 1994, 3% of cellular Raf is complexed with Ras. So raise kb 4x to 4e-5 This step needed to memb-anchor and activate Raf: Leevers et al Nature 369 411-414.
2	Ras-intrinsic-GT Pase	MAPK_MKP1_ oscillation Accession No. : 9	Ras Pathway No. : 63	0.0001 (s^-1)	0 (s^-1)	-	-	Substrate GTP-Ras Product GDP-Ras
	This is extremely slow (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 kf = 1e-4

Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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