NO binds to the distal site of haem in the fully activated soluble guanylate cyclase

• Published in: Nitric oxide Vol. 134-135; pp. 17 - 22
• Main Authors: Liu, Rui, Kang, Yunlu, Chen, Lei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2023
• Subjects: cGMP; Cyclic GMP - metabolism; Guanylate Cyclase - metabolism; Haem; Heme - chemistry; Nitric oxide; Nitric Oxide - metabolism; sGC; Soluble Guanylyl Cyclase; cGMP; Haem; Nitric oxide; sGC
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2023.03.002

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO). The binding of NO to the haem of sGC induces a large conformational change in the enzyme and activates its cyclase activity. However, whether NO binds to the proximal site or the distal site of haem in the fully activated state remains under debate. Here, we present cryo-EM maps of sGC in the NO-activated state at high resolutions, allowing the observation of the density of NO. These cryo-EM maps show the binding of NO to the distal site of haem in the NO-activated state. •Structures of human sGC α1β1 heterodimer in three states have been determined to 3.1–3.3 Å resolution.•One NO molecule binds to the distal site of haem in the fully activated state of sGC.•C517 of the α1 subunit and C78 and C122 of the β1 subunit of sGC are not S-nitrosylated in the fully activated state.