Abstract
We hereby report on a mutational analysis of a novel natriuretic peptide (PNP), recently isolated by us from the Iranian snake venom. The PNP variant (mutPNP) with four substitutions (G16T, K18S, R21S, G23R) and a disulfide bonded ring shortened by 3 residues. mutPNP peptide was expressed in pET32 and purified by affinity separation on nickel resin followed by RP-HPLC chromatography. The conformation of mutPNP was characterized in solution by 1H nuclear magnetic resonance spectroscopy, where it was found that the 14-residue disulfide bonded ring, like the 17- residue ring in PNP, retains a high degree of conformational flexibility. The conformation of mutPNP bound to NPR-C receptor was predicted by homology protein structure modeling. When injected intravenously into rats, mutPNP, in contrast to PNP had no physiological effect on blood pressure or on diuresis. The loss of physiological activity is explained in terms of the modeled bound conformation and the ensemble of solution conformations obtained using the NMR constraints.
Keywords: Natriuretic peptide, mutant, NMR, conformation, receptor binding, physiological effects
Protein & Peptide Letters
Title: Structural and Functional Characterization of a Mutant of Pseudocerastes persicus Natriuretic Peptide
Volume: 13 Issue: 3
Author(s): Maryam M. Elmi, Mehriar Amininasab, Takayuki Hondo, Jun Kikuchi, Yutaka Kuroda, Hossein Naderi-Manesh and Mohammad N. Sarbolouki
Affiliation:
Keywords: Natriuretic peptide, mutant, NMR, conformation, receptor binding, physiological effects
Abstract: We hereby report on a mutational analysis of a novel natriuretic peptide (PNP), recently isolated by us from the Iranian snake venom. The PNP variant (mutPNP) with four substitutions (G16T, K18S, R21S, G23R) and a disulfide bonded ring shortened by 3 residues. mutPNP peptide was expressed in pET32 and purified by affinity separation on nickel resin followed by RP-HPLC chromatography. The conformation of mutPNP was characterized in solution by 1H nuclear magnetic resonance spectroscopy, where it was found that the 14-residue disulfide bonded ring, like the 17- residue ring in PNP, retains a high degree of conformational flexibility. The conformation of mutPNP bound to NPR-C receptor was predicted by homology protein structure modeling. When injected intravenously into rats, mutPNP, in contrast to PNP had no physiological effect on blood pressure or on diuresis. The loss of physiological activity is explained in terms of the modeled bound conformation and the ensemble of solution conformations obtained using the NMR constraints.
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Cite this article as:
Elmi M. Maryam, Amininasab Mehriar, Hondo Takayuki, Kikuchi Jun, Kuroda Yutaka, Naderi-Manesh Hossein and Sarbolouki N. Mohammad, Structural and Functional Characterization of a Mutant of Pseudocerastes persicus Natriuretic Peptide, Protein & Peptide Letters 2006; 13 (3) . https://dx.doi.org/10.2174/092986606775338452
DOI https://dx.doi.org/10.2174/092986606775338452 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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