Structure and regulation of soluble guanylate cyclase.

Journal Article (Review;Journal Article)

Nitric oxide (NO) is an essential signaling molecule in biological systems. In mammals, the diatomic gas is critical to the cyclic guanosine monophosphate (cGMP) pathway as it functions as the primary activator of soluble guanylate cyclase (sGC). NO is synthesized from l-arginine and oxygen (O(2)) by the enzyme nitric oxide synthase (NOS). Once produced, NO rapidly diffuses across cell membranes and binds to the heme cofactor of sGC. sGC forms a stable complex with NO and carbon monoxide (CO), but not with O(2). The binding of NO to sGC leads to significant increases in cGMP levels. The second messenger then directly modulates phosphodiesterases (PDEs), ion-gated channels, or cGMP-dependent protein kinases to regulate physiological functions, including vasodilation, platelet aggregation, and neurotransmission. Many studies are focused on elucidating the molecular mechanism of sGC activation and deactivation with a goal of therapeutic intervention in diseases involving the NO/cGMP-signaling pathway. This review summarizes the current understanding of sGC structure and regulation as well as recent developments in NO signaling.

Full Text

Duke Authors

Cited Authors

  • Derbyshire, ER; Marletta, MA

Published Date

  • January 2012

Published In

Volume / Issue

  • 81 /

Start / End Page

  • 533 - 559

PubMed ID

  • 22404633

Electronic International Standard Serial Number (EISSN)

  • 1545-4509

International Standard Serial Number (ISSN)

  • 0066-4154

Digital Object Identifier (DOI)

  • 10.1146/annurev-biochem-050410-100030


  • eng