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Molecule Parameter List for GDP-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

GDP-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	2	1	0	1

Accession and Pathway Details

Accession Name	Accession No.	Accession Type	Pathway Link
MAPK-bistability -fig1c	35	Network	Shared_Object_MAPK-bistability-fig1c,  Sos,  PKC,   MAPK,  PLA2,  Ras,   PDGFR
Model for figure 1c in Bhalla US et al. Science (2002) 297(5583):1018-23. The demo for this figure is available here. This synaptic signaling model is without the MKP-1 feedback, so it is bistable and remains so over long periods.

GDP-Ras acting as a Molecule in  MAPK-bistability-fig1c Network

Name	Accession Name	Pathway Name	Initial Conc. (uM)	Volume (fL)	Buffered
GDP-Ras	MAPK-bistability -fig1c Accession No. : 35	Ras Pathway No. : 184	0.2	1000	No
GDP bound form. See Rosen et al Neuron 12 1207-1221 June 1994. the activation loop is based on Boguski and McCormick Nature 366 643-654 93 Assume Ras is present at about the same level as craf-1, 0.2 uM. Hallberg et al JBC 269:6 3913-3916 1994 estimate upto 5-10% of cellular Raf is assoc with Ras. Given that only 5-10% of Ras is GTP-bound, we need similar amounts of Ras as Raf.

GDP-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
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.

GDP-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
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.

GDP-Ras acting as a Product 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
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.