Stone1996 - activation of soluble guanylate cyclase by nitric oxide

ABSTRACT: 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: Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. 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. This model is hosted on BioModels Database and identified by: BIOMD0000000198. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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.

SUBMITTER: Sharat Vayttaden  

PROVIDER: BIOMD0000000198 | BioModels | 2008-10-21

REPOSITORIES: BioModels