Natriuretic peptides (NPs) are a family of structurally related hormone/paracrine factors (ANP, BNP and CNP), which mediate a broad array of physiological effects by interacting with specific guanylyl cyclase receptors (NPR) and have promising therapeutic and clinical applications. NPs are specific for different NPRs and share a common ring structure in which a disulfide bond between two conserved cysteine residues is formed. Residues within the cyclic loop are largely responsible for receptor selectivity. Structural features of free NPs in solution have not been investigated in details even if their characterization would be very useful in order to identify important aspects related to NPs function and receptor selectivity. In light of the above scenario, we carried out a 0.1 mu s molecular dynamics investigation of NPs with the aim of providing a high-resolution atomistic view of specific of their conformational ensemble in solution. Our results clearly indicate that NP receptor-bound conformations are not stable solution structure and that induced-fit mechanisms are involved in the formation of NP-NPR complexes. Moreover, in agreement with the current view on strictly relationship between protein dynamics and protein function and activity, it turns out that differences in activity and NPR specificity of CNP and ANP/BNP might be correlated to different amino acid composition of the cyclic loop, propensity to form beta-sheet structures, flexibility patterns, dynamics properties and free conformations explored during the simulations. (C) 2010 Elsevier Inc. All rights reserved.

Papaleo, E., Russo, L., Shaikh, N., Cipolla, L., Fantucci, P., DE GIOIA, L. (2010). Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 28(8), 834-841 [10.1016/j.jmgm.2010.03.003].

Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity

RUSSO, LAURA;CIPOLLA, LAURA FRANCESCA;FANTUCCI, PIERCARLO;DE GIOIA, LUCA
2010

Abstract

Natriuretic peptides (NPs) are a family of structurally related hormone/paracrine factors (ANP, BNP and CNP), which mediate a broad array of physiological effects by interacting with specific guanylyl cyclase receptors (NPR) and have promising therapeutic and clinical applications. NPs are specific for different NPRs and share a common ring structure in which a disulfide bond between two conserved cysteine residues is formed. Residues within the cyclic loop are largely responsible for receptor selectivity. Structural features of free NPs in solution have not been investigated in details even if their characterization would be very useful in order to identify important aspects related to NPs function and receptor selectivity. In light of the above scenario, we carried out a 0.1 mu s molecular dynamics investigation of NPs with the aim of providing a high-resolution atomistic view of specific of their conformational ensemble in solution. Our results clearly indicate that NP receptor-bound conformations are not stable solution structure and that induced-fit mechanisms are involved in the formation of NP-NPR complexes. Moreover, in agreement with the current view on strictly relationship between protein dynamics and protein function and activity, it turns out that differences in activity and NPR specificity of CNP and ANP/BNP might be correlated to different amino acid composition of the cyclic loop, propensity to form beta-sheet structures, flexibility patterns, dynamics properties and free conformations explored during the simulations. (C) 2010 Elsevier Inc. All rights reserved.
Articolo in rivista - Articolo scientifico
Cyclic peptide; Dynamics and function conservation; Free energy landscape; Molecular dynamics; Natriuretic peptide;
English
2010
28
8
834
841
none
Papaleo, E., Russo, L., Shaikh, N., Cipolla, L., Fantucci, P., DE GIOIA, L. (2010). Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 28(8), 834-841 [10.1016/j.jmgm.2010.03.003].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/16917
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