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Molecule Parameter List for CaNAB-Ca4

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
CaNAB-Ca4 participated asMoleculeSum total ofEnzymeSubstrate of an enzymeProduct of an enzymeSubstrate in ReactionProduct in Reaction
No. of occurrences1010031

Accession and Pathway Details
Accession NameAccession No.Accession TypePathway Link
  • Synaptic_
    Network
  • 16Network
    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

    CaNAB-Ca4 acting as a Molecule in  
    Synaptic_Network Network
    NameAccession NamePathway NameInitial Conc.
    (uM)
    Volume
    (fL)
    Buffered
    CaNAB-Ca4
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 01000No
    Four calciums bound to CaN. This has an activity in absence of CaM. Perrino et al 1992 JBC 267(22):15965-15969

    CaNAB-Ca4 acting as an Enzyme in  
    Synaptic_Network Network
    Enzyme Molecule /
    Enzyme Activity
    Accession NamePathway NameKm (uM)kcat (s^-1)RatioEnzyme TypeReagents
    CaNAB-Ca4 /
  • dephosph_
    inhib1_noCaM
  • Synaptic_
    Network

    Accession No. : 16
  • Shared_Object_
    Synaptic_
    Network

    Pathway No. : 70
  • 4.970760.0344explicit E-S complexSubstrate
    I1*

    Product
    I1
    The rates here are so slow I do not know if we should even bother with this enzyme reaction. These numbers are from Liu and Storm JBC 1989 264(22):12800-12804 They say that the CaM-free form of CaN operates at about the same Km of 5 uM, but at a much lower Vmax of 1 nmol/min/mg. Other estimates of activity without CaM suggest 10% activity, which is what I use here.

    CaNAB-Ca4 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.
     NameAccession NamePathway NameKfKbKdtauReagents
    1
  • CaM-Ca2-bind-CaN
    AB
  • Synaptic_
    Network

    Accession No. : 16
  • PP2B
    Pathway No. : 83
    0.24
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 4.1667(uM)-Substrate
    CaM-TR2-Ca2
    CaNAB-Ca4

    Product
    CaMCa2-CANAB
      Based on Stemmer and Klee 1994 Biochem 33:6859-6866 This model is actually a simplification of the detail they report. In this model the Ca-binding affinity of CaM is not changed by binding to CaN. Rates here come from a detailed-balance argument. The reference rate is for CaMCa4 binding to CaNAB. This rate should be 1/2500 of that.
    2
  • CaMCa3-bind-CaNA
    B
  • Synaptic_
    Network

    Accession No. : 16
  • PP2B
    Pathway No. : 83
    2.238
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 0.4468(uM)-Substrate
    CaM-Ca3
    CaNAB-Ca4

    Product
    CaMCa3-CaNAB
      Rates derived from the CaMCa4 binding to CaNAB-Ca4 step. Due to detailed balance calculations taking the Ca affinity for CaM into account, this reaction should be 250 times slower. Close.
    3
  • CaMCa4-bind-CaNA
    B
  • Synaptic_
    Network

    Accession No. : 16
  • PP2B
    Pathway No. : 83
    600
    (uM^-1 s^-1)
    1
    (s^-1)
    Kd(bf) = 0.0017(uM)-Substrate
    CaM-Ca4
    CaNAB-Ca4

    Product
    CaMCa4-CaNAB
      This step is the starting point for calculating all the CaM-binding steps to CaNAB-Ca4. The calculation goes like this: From Stemmer and Klee 1994 Biochem 33 6859-6866 we have rates for Ca binding to CaM.Ca4.CaN. From detailed balance (Kd must be 1 around a loop) we can set ratios of Kds for CaMCa3 binding to CaN, and CaM-Ca2 binding to CaN. Thus those rates can come once we know the Kd for the current reaction of CaMCa4 binding to CaN. We'll ignore the Ca binding steps to CaM.Ca4.CaN since the reactions around the remaining part of the loop will settle pretty fast to the same levels. Finally, we estimate the kf=0.001 here from a series of simulations matching the curves in Stemmer and Klee.

    CaNAB-Ca4 acting as a Product 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.
    NameAccession NamePathway NameKfKbKdtauReagents
  • Ca-bind-CaNAB-Ca
    2
  • Synaptic_
    Network

    Accession No. : 16
  • PP2B
    Pathway No. : 83
    3.6
    (uM^-2 s^-1)
    1
    (s^-1)
    Kd(af) = 0.527(uM)-Substrate
    Ca
    Ca
    CaNAB-Ca2

    Product
    CaNAB-Ca4
    This process is probably much more complicated and involves CaM. However, as I can't find detailed info I am bundling this into a single step. Based on Steemer and Klee 1994 Biochem 33:6859-6866, this specific parm on pg 6863, the Kact is 0.5 uM. Assume binding is fast, 1 sec.



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