BRaf and Raf1-Activation

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Binding Reaction


BRaf-Activation:

  \text{BRaf} + \text{activeRap1} \rightleftharpoons \text{BRafPP} + \text{activeRap1}

Raf1-Activation:

 \text{Raf1} + \text{activeRas}  \rightleftharpoons \text{Raf1PP} + \text{activeRas}


Kinetic equation


BRaf-Activation:

v_{\text{BRaf-Activation}} = \frac{k_{cat} \cdot [\text{activeRap1}] \cdot [\text{BRaf}] \cdot (1-\frac{[\text{BRafPP}]}{[\text{BRaf}] \cdot K_{eq}})}{Km_{\text{BRaf}} \cdot (1 + \frac{[\text{BRaf}]}{Km_{\text{BRaf}}} + \frac{[\text{BRafPP}]}{Km_{\text{BRafPP}}})}

The activation of BRaf by Ras is modelled in the same way as the one by Rap1.

Raf1-Activation:

v_{\text{Raf1-Activation}} = \frac{k_{cat} \cdot [\text{activeRas}] \cdot [\text{Raf1}] \cdot (1-\frac{[\text{Raf1PP}]}{[\text{Raf1}] \cdot K_{eq}})}{Km_{\text{Raf1}} \cdot (1 + \frac{[\text{Raf1}]}{Km_{\text{Raf1}}} + \frac{[\text{Raf-1PP}]}{Km_{\text{Raf1PP}}})}


final Parameter

Raf1 BRaf (Rap1) BRaf (Ras)
kcat [1/s]
mean [1/s] 17.658 17.2111 5.85846
std [1/s] 3.0997 3.0213 1.0284
Km [μM]
mean [μM] 5.42275 * 109 9.66527 * 109 2.43218 * 109
std [μM] 2.6674 * 109 4.5458 * 109 1.1439 * 109

Parameter

The same values as in the model by Xu et al (2010)[1] are used and the standard deviation is calculated by assuming the same averaged relative error as for the measured values.(Calculation of the averaged relative error)

KmP value and equilibrium constant

The Km value for the product is assumed to be similar to but slightly smaller than the the Km value of the substrate because of the similarity of the both species. Therefore the Km value of the substrate is multiplied by 0.95 to gain the one of the product and the uncertainty is increased by increasing the error on Kmsubstrate by 50%.

For information about the equilibrium constant please see here.

References

  1. Tian-Rui Xu et al. (2010) "Inferring signaling pathway topologies from multiple perturbation measurements of specific biochemical species." Sci Signal. 3(134):ra20. (pmid:20234003)