8s9y

Taipan Natriuretic Peptide C -TNPcTaipan Natriuretic Peptide C -TNPc

Structural highlights 8s9y is a 1 chain structure with sequence from Oxyuranus microlepidotus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VNPC_OXYMI Snake venom natriuretic peptide that exhibits vasoactive and hypotensive activity (By similarity). Produces a near complete relaxation in pre-contracted aortae by activating the natriuretic peptide receptor 1 (NPR1) (PubMed:15652496). Stimulates cGMP production through the natriuretic peptide receptor 1 (NPR1) with high potencies for the rat NPR1 (EC(50)=100 nM), and very weak potencies over human NPR1 (28% activation at 10 uM) (PubMed:37049825). In vivo, reduces both systolic and diastolic blood pressure with no effect on heart rate, when intravenously injected in conscious rabbits (PubMed:37049825). Also enhances the bradycardia due to cardiac afferent stimulation (Bezold-Jarisch reflex) (PubMed:37049825).[UniProtKB:C6EVG7] Publication Abstract from PubMed Cardiovascular ailments are a major cause of mortality where over 1.3 billion people suffer from hypertension leading to heart-disease related deaths. Snake venoms possess a broad repertoire of natriuretic peptides with therapeutic potential for treating hypertension, congestive heart failure, and related cardiovascular disease. We now describe several taipan (Oxyuranus microlepidotus) natriuretic peptides TNPa-e which stimulated cGMP production through the natriuretic peptide receptor A (NPR-A) with higher potencies for the rat NPR-A (rNPR-A) over human NPR-A (hNPR-A). TNPc and TNPd were the most potent, demonstrating 100- and 560-fold selectivity for rNPR-A over hNPR-A. In vivo studies found that TNPc decreased diastolic and systolic blood pressure (BP) and increased heart rate (HR) in conscious normotensive rabbits, to a level that was similar to that of human atrial natriuretic peptide (hANP). TNPc also enhanced the bradycardia due to cardiac afferent stimulation (Bezold-Jarisch reflex). This indicated that TNPc possesses the ability to lower blood pressure and facilitate cardiac vagal afferent reflexes but unlike hANP does not produce tachycardia. The 3-dimensional structure of TNPc was well defined within the pharmacophoric disulfide ring, displaying two turn-like regions (RMSD = 1.15 A). Further, its much greater biological stability together with its selectivity and potency will enhance its usefulness as a biological tool. Taipan Natriuretic Peptides Are Potent and Selective Agonists for the Natriuretic Peptide Receptor A.,Vink S, Akondi KB, Jin J, Poth K, Torres AM, Kuchel PW, Burke SL, Head GA, Alewood PF Molecules. 2023 Mar 29;28(7):3063. doi: 10.3390/molecules28073063. PMID:37049825 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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