A novel insight into the molecular mechanism of human soluble guanylyl cyclase focused on catalytic domain in living cells.
Biochem Biophys Res Commun
; 604: 51-56, 2022 05 14.
Article
em En
| MEDLINE
| ID: mdl-35290760
ABSTRACT
Human soluble guanylate cyclase (sGC) is a heme-containing metalloprotein in NO-sGC-cGMP signaling. In this work, fluorescent proteins were employed to study the NO-induced sGC molecular mechanism via mutagenesis at the catalytic domain. The conformational change of sGC by mutant α1C595 was investigated in living cells through fluorescence lifetime imaging microscopy (FLIM). The results indicated that the NO-induced conformational change of the catalytic domain of sGC from "open to "closed" upon GTP-binding was regulated by the hydrogen (H)-bonding network of the catalytic domain. The mutation of C595 caused a big conformational change of catalytic domain with H-bond variation, which not only demonstrates the key role of the C595 site in the process of conformational change of the catalytic domain, but also reveals the regulatory mechanism of sGC at the catalytic domain. This finding would guide the design of small-molecule drugs targeting the catalytic domain to modulate sGC activity.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Citoplasmáticos e Nucleares
/
Guanilato Ciclase
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article