7d9s

Structure of huamn soluble guanylate cyclase in the YC1 and NO-bound state

spinqualitylabelsall models 7d9s, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7d9s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: G2P, HEM, MG, YC1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GCYA1_HUMAN Moyamoya disease with early-onset achalasia. The disease is caused by mutations affecting the gene represented in this entry. Function GCYA1_HUMAN Publication Abstract from PubMed Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) in human. It is an important validated drug target for cardiovascular diseases. sGC can be pharmacologically activated by stimulators and activators. However, the detailed structural mechanisms, through which sGC is recognized and positively modulated by these drugs at high spacial resolution, are poorly understood. Here, we present cryo-electron microscopy structures of human sGC in complex with NO and sGC stimulators, YC-1 and riociguat, and also in complex with the activator cinaciguat. These structures uncover the molecular details of how stimulators interact with residues from both beta H-NOX and CC domains, to stabilize sGC in the extended active conformation. In contrast, cinaciguat occupies the haem pocket in the beta H-NOX domain and sGC shows both inactive and active conformations. These structures suggest a converged mechanism of sGC activation by pharmacological compounds. Activation mechanism of human soluble guanylate cyclase by stimulators and activators.,Liu R, Kang Y, Chen L Nat Commun. 2021 Sep 17;12(1):5492. doi: 10.1038/s41467-021-25617-0. PMID:34535643 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Guanylate cyclase 3D structures

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