8S9Y

Taipan Natriuretic Peptide C -TNPc

Summary for 8S9Y

• Entry DOI: 10.2210/pdb8s9y/pdb
• NMR Information: BMRB: 31076
• Descriptor: Peptide TNP-c (1 entity in total)
• Functional Keywords: defined ring region, toxin
• Biological source: Oxyuranus microlepidotus
• Total number of polymer chains: 1
• Total formula weight: 4119.69

Authors

Torres, A.M.,Alewood, P.F. (deposition date: 2023-03-30, release date: 2023-04-12, Last modification date: 2024-10-16)

Primary citation

Vink, S.,Akondi, K.B.,Jin, J.,Poth, K.,Torres, A.M.,Kuchel, P.W.,Burke, S.L.,Head, G.A.,Alewood, P.F.
Taipan Natriuretic Peptides Are Potent and Selective Agonists for the Natriuretic Peptide Receptor A.
Molecules, 28:-, 2023

PubMed Abstract: 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 () 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 Å). Further, its much greater biological stability together with its selectivity and potency will enhance its usefulness as a biological tool.

PubMed: 37049825
DOI: 10.3390/molecules28073063

Experimental method

SOLUTION NMR