Calcium ion downregulates soluble guanylyl cyclase activity: evidence for a two-metal ion catalytic mechanism.
Arch Biochem Biophys
; 387(1): 47-56, 2001 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-11368183
ABSTRACT
The inhibition of soluble guanylyl cyclase by Ca2+ has been kinetically characterized and the results support a two-metal-ion catalytic mechanism for formation of cGMP. Ca2+ reversibly inhibits both the basal and NO-stimulated forms of bovine lung soluble guanylyl cyclase. Inhibition is independent of the activator identity and concentration, revealing that Ca2+ interacts with a site independent of the heme regulatory site. Inhibition by Ca2+ is competitive with respect to Mg2+ in excess of substrate, with Kis values of 29 +/- 4 and 6.6 +/- 0.6 microM for the basal and activated states, respectively. Ca2+ inhibits noncompetitively with respect to the substrate MgGTP in both activity states. The qualitatively similar inhibition pattern and quantitatively different Ki values between the basal and NO-stimulated states suggest that the Ca2+ binding site undergoes some structural modification upon activation of the enzyme. The competitive nature of Ca2+ inhibition with respect to excess Mg2+ is consistent with a two-metal-ion mechanism for cyclization.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
GMP Cíclico
/
Guanilato Ciclasa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Arch Biochem Biophys
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos