STRUCTURE-FUNCTION RELATIONSHIPS AND ACTION MECHANISM OF KRAIT NATRIURETIC PEPTIDE

Abstract

Endogenous natriuretic peptides (NPs) are a class of potent vasoactive hormones, which maintain pressure-volume homeostasis. Snake venom NPs are structurally similar to endogenous NPs with a 17-residue ring but with variable C-terminal extension. In the present study, a unique NP from a krait , KNP, has been studied. Structurally, KNP has a 38-residue long C-terminal tail which has propensity to form a-helix. KNP induced vasorelaxation of aortic strip by a mechanism independent of NP receptors in contrast to canonical NPs. Deletion mutant study has revealed the presence of two functional pharmacophores; KNP ring and putative helix. Ring functions like a classical NP while Helix induces vasorelaxation in NP receptor independent manner like KNP. Thus, the helical segment in KNP?s C-tail seems to confer its bio-activity. KNP showed remarkable resistance (half-life >150 min) to degradation by neural endopeptidase. By specific substitutions, the key residues involved in conferring resistance have been identified.