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BIOMD0000000198 - Stone1996 - activation of soluble guanylate cyclase by nitric oxide

 

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Reference Publication
Publication ID: 8573563
Stone JR, Marletta MA.
Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide.
Biochemistry 1996 Jan; 35(4): 1093-1099
Department of Biological Chemistry, School of Medicine, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.  [more]
Model
Original Model: DOQCS logo
Submitter: Sharat Vayttaden
Submission ID: MODEL4779732381
Submission Date: 24 Oct 2008 14:11:14 UTC
Last Modification Date: 03 Mar 2017 16:40:15 UTC
Creation Date: 21 Oct 2008 15:19:25 UTC
Encoders:  Lukas Endler
   Vijayalakshmi Chelliah
   James R Stone
   Michael A Marletta
set #1
bqbiol:hasTaxon Taxonomy Bos taurus
bqbiol:isVersionOf Gene Ontology regulation of guanylate cyclase activity
Gene Ontology nitric oxide mediated signal transduction
Notes
Stone1996 - activation of soluble guanylate cyclase by nitric oxide
This features the two step binding of NO to soluble Guanylyl Cyclase as proposed by Stone JR, Marletta MA. Biochemistry (1996) 35(4):1093-9 . There is a fast step binding scheme and a slow step binding scheme. The difference lies in the binding of a NO to a non-heme site on sGC, which may not necessarily be the same site of binding during the initial binding. The rates have been directly used models.

This model is described in the article:

Stone JR, Marletta MA.
Biochemistry 1996 Jan; 35(4): 1093-1099

Abstract:

The soluble form of guanylate cyclase (sGC) is the only definitive receptor for the signaling agent nitric oxide (.NO). The enzyme is a heterodimer of homologous subunits in which each subunit binds 1 equiv of 5-coordinate high-spin heme. .NO increases the Vmax of sGC up to 400-fold and has previously been shown to bind to the heme to form a 5-coordinate complex. Using stopped-flow spectrophotometry, it is demonstrated that the binding of .NO to the heme of sGC is a complex process. .NO first binds to the heme to form a 6-coordinate nitrosyl complex, which then converts to a 5-coordinate nitrosyl complex through one of two ways. For 28 +/- 4% of the heme, the 6-coordinate nitrosyl complex rapidly (approximately 20 s-1) converts to the 5-coordinate complex. For the remaining 72 +/- 4% of the heme, the conversion of the 6-coordinate nitrosyl complex to a 5-coordinate nitrosyl complex is slow (0.1-1.0 s-1) and is dependent upon the interaction of .NO with an unidentified non-heme site on the protein. The heme (200 nM) was completely converted to the 5-coordinate state with as little as 500 nM .NO, and the equilibrium dissociation constant of .NO for activating the enzyme was determined to be < or = 250 nM. Gel-filtration analysis indicates that the binding of .NO to the heme has no effect on the native molecular mass of the protein. Correlation of electronic absorption spectra with activity measurements indicates that the 5-coordinate nitrosyl form of the enzyme is activated relative to the resting 5-coordinate ferrous form of the enzyme.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 8573563 Submission Date: 24 Oct 2008 14:11:14 UTC Last Modification Date: 03 Mar 2017 16:40:15 UTC Creation Date: 21 Oct 2008 15:19:25 UTC
Mathematical expressions
Reactions
r1fast r2fast r3fast r1slow
r2slow r3slow r4slow  
Rules
Assignment Rule (variable: NO_sGC_5coord_tot) Assignment Rule (variable: sGC_inact_tot) Assignment Rule (variable: extinction)  
Physical entities
Compartments Species
cytosol NO sGCfast NO_sGCfast
NO_sGCfast_6coord NO_sGCfast_5coord sGCslow
NO_sGCslow NO_sGCslow_6coord NO_sGCslow_6coord_NO_int
NO_sGCslow_5coord NO_sGC_5coord_tot sGC_inact_tot
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
ext_5coord ext_5coord_NO ext_6coord_NO extinction
Reactions (7)
 
 r1fast [NO] + [sGCfast] ↔ [NO_sGCfast];  
 
 r2fast [NO_sGCfast] → [NO_sGCfast_6coord];  
 
 r3fast [NO_sGCfast_6coord] ↔ [NO_sGCfast_5coord];  
 
 r1slow [NO] + [sGCslow] ↔ [NO_sGCslow];  
 
 r2slow [NO_sGCslow] → [NO_sGCslow_6coord];  
 
 r3slow [NO] + [NO_sGCslow_6coord] ↔ [NO_sGCslow_6coord_NO_int];  
 
 r4slow [NO_sGCslow_6coord_NO_int] ↔ [NO_sGCslow_5coord];  
 
Rules (3)
 
 Assignment Rule (name: NO_sGC_5coord_tot) NO_sGC_5coord_tot = NO_sGCfast_5coord+NO_sGCslow_5coord
 
 Assignment Rule (name: sGC_inact_tot) sGC_inact_tot = sGCfast+NO_sGCfast+NO_sGCfast_6coord+sGCslow+NO_sGCslow+NO_sGCslow_6coord+NO_sGCslow_6coord_NO_int
 
 Assignment Rule (name: ext) extinction = e5c*(sGCfast+NO_sGCfast+sGCslow+NO_sGCslow)+e5c_NO*(NO_sGCfast_5coord+NO_sGCslow_5coord)+e6c_NO*(NO_sGCfast_6coord+NO_sGCslow_6coord+NO_sGCslow_6coord_NO_int)
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 NO
Compartment: cytosol
Initial concentration: 0.5
 
 sGCfast
Compartment: cytosol
Initial concentration: 0.112
 
 NO_sGCfast
Compartment: cytosol
Initial concentration: 0.0
 
 NO_sGCfast_6coord
Compartment: cytosol
Initial concentration: 0.0
 
 NO_sGCfast_5coord
Compartment: cytosol
Initial concentration: 0.0
 
 sGCslow
Compartment: cytosol
Initial concentration: 0.288
 
 NO_sGCslow
Compartment: cytosol
Initial concentration: 0.0
 
 NO_sGCslow_6coord
Compartment: cytosol
Initial concentration: 0.0
 
 NO_sGCslow_6coord_NO_int
Compartment: cytosol
Initial concentration: 0.0
 
 NO_sGCslow_5coord
Compartment: cytosol
Initial concentration: 0.0
 
  NO_sGC_5coord_tot
Compartment: cytosol
Initial concentration: 0.0
 
  sGC_inact_tot
Compartment: cytosol
Initial concentration: 0.0
 
Global Parameters (16)
 
   k1
Value: 700.0   (Units: peruMpersec)
Constant
 
   k2
Value: 800.0   (Units: persec)
Constant
 
   k3
Value: 850.0   (Units: persec)
Constant
 
   k4
Value: 20.0   (Units: persec)
Constant
 
   k5
Value: 0.2   (Units: persec)
Constant
 
   k6
Value: 700.0   (Units: peruMpersec)
Constant
 
   k7
Value: 800.0   (Units: persec)
Constant
 
   k8
Value: 850.0   (Units: persec)
Constant
 
   k9
Value: 5.0   (Units: peruMpersec)
Constant
 
   k10
Value: 25.0   (Units: persec)
Constant
 
   k11
Value: 1.6   (Units: persec)
Constant
 
   k12
Value: 0.02   (Units: persec)
Constant
 
 ext_5coord
Value: 0.11   (Units: peruMpercm)
Constant
 
 ext_5coord_NO
Value: 0.025   (Units: peruMpercm)
Constant
 
 ext_6coord_NO
Value: 0.064   (Units: peruMpercm)
Constant
 
  extinction
Value: NaN   (Units: percm)
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000198

Curator's comment: (updated: 03 Mar 2017 16:13:04 GMT)

Figure 4A of the reference publication has been reproduced here. The model was simulated using SBML odeSolver (102008). It seems a pathlength of 0.5cm was used for simulations in the article, as dividing the results by 2 gives the results in the article.

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