{"@type": "dcat:Dataset", "accessLevel": "public", "bureauCode": ["009:25"], "contactPoint": {"@type": "vcard:Contact", "fn": "NIH", "hasEmail": "mailto:info@nih.gov"}, "description": "Background\n          The most important receptor for nitic oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase.\n        \n        \n          Results\n          We developed a photoaffinity label (3H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of 3H-meta-PAL together with the highly purified sGC leads to a covalent binding to the \u03b11-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the 3H-meta-PAL labeled sGC was fragmented by CNBr digest. The 3H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236\u2013290 of the \u03b11-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the 3H-meta-PAL.\n        \n        \n          Conclusions\n          Our data demonstrate that the region surrounding the cysteines 238 and 243 in the \u03b11-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators.", "distribution": [{"@type": "dcat:Distribution", "description": "Visit the original government dataset for complete information, documentation, and data access.", "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC64637/", "mediaType": "text/html", "title": "Official Government Data Source"}], "identifier": "https://healthdata.gov/api/views/5eea-9cyt", "issued": "2025-07-14", "keyword": ["bay-41-2272", "nih", "nitric-oxide-receptor", "soluble-guanylate-cyclase", "vasodilatation"], "landingPage": "https://healthdata.gov/d/5eea-9cyt", "modified": "2025-09-06", "programCode": ["009:048"], "publisher": {"@type": "org:Organization", "name": "National Institutes of Health"}, "theme": ["NIH"], "title": "NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272"}