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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 asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1004101

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning
  • 77Network
    Shared_Object_Ajay_Bhalla_2004_PKM_MKP3_Tuning PKC PLA2 
    PLCbeta Ras Gq 
    MAPK EGFR Sos 
    PLC_g CaMKII CaM 
    PP1 PP2B PKA 
    AC MKP3 PKM 
    This model is based on Ajay SM, Bhalla US. Eur J Neurosci. 2004 Nov;20(10):2671-80. This is the feedforward model with MPK3 from figure 8a.

    GDP-Ras acting as a Molecule in  
    Ajay_Bhalla_2004_PKM_MKP3_Tuning Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    GDP-Ras
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    0.51.5No
    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  
    Ajay_Bhalla_2004_PKM_MKP3_Tuning Network
     Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    1GEF-Gprot-bg  /
    GEF-bg_act-ras
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    0.5050510.024explicit E-S complexSubstrate
    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
    2GEF*  /
    GEF*-act-ras
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg-act-ras
    3CaM-GEF  /
    CaM-GEF-act-ras
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
        Kinetics same as GEF-bg_act-ras
    4Shc*.Sos.Grb2  /
    Sos.Ras_GEF
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Shared_Object_
    Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Pathway No. : 329
  • 0.5050510.024explicit E-S complexSubstrate
    GDP-Ras

    Product
    GTP-Ras
       

    GDP-Ras acting as a Product of an Enzyme in  
    Ajay_Bhalla_2004_PKM_MKP3_Tuning Network
    Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    GAP  /
    GAP-inact-ras
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    1.01039104explicit E-S complexSubstrate
    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) 5 Nov 2002: Changed ratio term to 4 from 100. Now we have k1=8.25e-5; k2=40, k3=10. k3 is still rate-limiting.

    GDP-Ras acting as a Product in a reaction in  
    Ajay_Bhalla_2004_PKM_MKP3_Tuning 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.
    NameAccession NamePathway NameKfKbKdtauReagents
  • Ras-intrinsic-GT
    Pase
  • Ajay_Bhalla_
    2004_PKM_MKP3_
    Tuning

    Accession No. : 77
  • Ras
    Pathway No. : 333
    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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