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Molecule Parameter List for cGK | 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 |
| cGK 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 | 0 | 0 | 1 | 0 |
Accession and Pathway Details | |
| Accession Name | Accession No. | Accession Type | Pathway Link | | cGMP_regulation | 34 | Network |
Shared_Object_cGMP_regulation, GC, PDE | Though Corbin JD. et al. Eur J Biochem. (2000) 267(9):2760-7 has been mentioned in the citation, this model has been made with inputs from different literature sources, each of which has been mentioned in the notes sections. This model features hydrolysis of cGMP by bovine PDE, phosphorylation of PDE by bovine lung PKG, and activation of bovine lung PKG by cGMP binding. These mechanisms are known to be involved in cGMP level regulation. Rates have been used from different sources and the model has been tested based on Corbin JD. et al., since their work involved measuring the PDE phosphorylation and PDE activity.
On replicating Figures 2, 3 and 4 from their paper, there is approx 30% difference in results but the qualitative shape of the curves is very similar. This might be due to the fact that the Vmax values were used from different literature sources. This might lead to the discrepancy in the numbers in this model. The values shown in this model are near estimated physiological levels.In order to replicate the Figures more closely, we have run additional simulations with concentration terms changed so as to replicate the experimental conditions exactly. |
cGK acting as a Molecule in cGMP_regulation Network
| Name | Accession Name | Pathway Name | Initial Conc.
(uM) | Volume
(fL) | Buffered | | cGK | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 1.1 | 0.0016667 | No | | cGMP dependent protein kinase (also cGKI and cGKII) They are both present in the brain. While cGKI is selectively present only in the Purkinje cells of the cerebellum, cGKII is widely expressed in the brain tissue and may be a neuronal target of cGMP. (El-Husseini et al., J Neurochem, 1995;64:2814; Hofmann et al., 2000, J Cell Sci, 113:1671-1676; Lohmann et al., 1997, Trends Biochem Sci, 22:307-312). PKG is a dimer, though the function of dimerization is not known, with some reports indicating that dimerization may not play a vital role in the activity of the enzyme. This is the inactive form, which on being bound by cGMP becomes active. The binding sites are described by their distinct rates of dissociation of bound cyclic nucleotide (fast and slow). - Taylor et al., 2000,JBC, 275(36):28053-28062. Intracellular concentration of PKG estimated to be present in vascular smooth muscle cells is around 0.3 - 0.5 uM. (Corbin et al., 2000, Eur J Biochem,267:2760-2767) |
cGK acting as a Substrate in a reaction in cGMP_regulation 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 | | cGMPbindcGK | cGMP_regulation
Accession No. : 34 | PDE
Pathway No. : 178 | 10
(uM^-1 s^-1) | 81
(s^-1) | Kd(bf) = 8.1(uM) | - | Substrate
cGK
cGMP
Product
cGMP.PKG
| | Kinase activation in both the isoforms of cGK depends on cyclic nucleotide occupation of the two cyclic nucleotide binding sites in the regulatory domain. This event is supposed to reduce the affinity of the auto-inhibition region of the regulatory domain for the catalytic domain. Investigations revealed that cGMP binds to a slowly dissociating cyclic nucleotide binding site and induces a conformational change resulting in a partially active kinase. Subsequent occupation of the second, rapid dissociation site imparts additional conformational change until it forms the elongated shape that is reported to be associated with the fully active enzyme. (Taylor et al., 2000, JBC, 275(36):28053-28062) Dissociation rates for cGKII binding sites from Taylor et al., 2000, and other refs cited in their paper. cGMP dissociation from slow site -- 8.1/s (Smith et al., JBC,1995, 271(34):20756-20762) |
| Database compilation and code copyright (C) 2022, Upinder S. Bhalla and NCBS/TIFR
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