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Sensitizing soluble guanylyl cyclase to become a highly CO‐sensitive enzyme.
Author(s) -
Friebe A.,
Schultz G.,
Koesling D.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb01078.x
Subject(s) - soluble guanylyl cyclase , activator (genetics) , guanylate cyclase , enzyme , chemistry , biochemistry , receptor
It took at least a decade to realize that the toxic gas NO is the physiological activator of soluble guanylyl cyclase (sGC), thereby acting as a signaling molecule in the nervous and cardiovascular systems. Despite its rather poor sGC‐activating property, CO has also been implicated as a physiological stimulator of sGC in neurotransmission and vasorelaxation. Here, we establish YC‐1 as a novel NO‐independent sGC activator that potentiates both CO‐ and NO‐induced sGC stimulation. As this potentiating effect is also observed with protoporphyrin IX which activates sGC independently of a gaseous ligand, we conclude that stabilization of the enzyme's active configuration is the underlying mechanism of YC‐1′s action. Moreover, the results obtained with YC‐1 reveal that CO is capable of stimulating sGC to a degree similar to NO, and thus provide the molecular basis for CO functioning as a signaling molecule.