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

Rui Liu; Yunlu Kang; Lei Chen

doi:10.1016/j.niox.2023.03.002

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

Nitric Oxide. 2023 May 1:134-135:17-22. doi: 10.1016/j.niox.2023.03.002. Epub 2023 Mar 25.

Authors

Rui Liu¹, Yunlu Kang¹, Lei Chen²

Affiliations

¹ State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, 100871, China; National Biomedical Imaging Center, Peking University, Beijing, 100871, China.
² State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Beijing, 100871, China; National Biomedical Imaging Center, Peking University, Beijing, 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China. Electronic address: chenlei2016@pku.edu.cn.

PMID: 36972843
DOI: 10.1016/j.niox.2023.03.002

Abstract

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.

Keywords: Haem; Nitric oxide; cGMP; sGC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cyclic GMP / metabolism
Guanylate Cyclase* / metabolism
Heme / chemistry
Nitric Oxide* / metabolism
Soluble Guanylyl Cyclase

Substances

Soluble Guanylyl Cyclase
Nitric Oxide
Guanylate Cyclase
Heme
Cyclic GMP