ATP potentiates competitive inhibition of guanylyl cyclase A and B by the staurosporine analog, Gö6976: reciprocal regulation of ATP and GTP binding.
J Biol Chem
; 286(39): 33841-4, 2011 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-21828054
ABSTRACT
Natriuretic peptides and ATP activate and Gö6976 inhibits guanylyl cyclase (GC)-A and GC-B. Here, the mechanism of inhibition was determined. Gö6976 progressively increased the Michaelis-Menten constant and decreased the Hill coefficient without reducing the maximal velocity of GC-A and GC-B. In the presence of 1 mm ATP, the K(i) was 1 µm for both enzymes. Inhibition of GC-B was minimal in the absence of ATP, and 1 mm ATP increased the inhibition 4-fold. In a reciprocal manner, 10 µm Gö6976 increased the potency of ATP for GC-B 4-fold. In contrast to a recent study (Duda, T., Yadav, P., and Sharma, R. K. (2010) FEBS J. 277, 2550-2553), neither staurosporine nor Gö6976 activated GC-A or GC-B. This is the first study to show that Gö6976 reduces GTP binding and the first demonstration of a competitive inhibitor of a receptor guanylyl cyclase. We conclude that Gö6976 reduces GTP binding to the catalytic site of GC-A and GC-B and that ATP increases the magnitude of the inhibition.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carbazóis
/
Trifosfato de Adenosina
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Receptores do Fator Natriurético Atrial
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Inibidores Enzimáticos
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Guanosina Trifosfato
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article