2fly

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Proadrenomedullin N-Terminal 20 Peptide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The preferred conformation of Proadrenomedullin N-Terminal 20 Peptide, (PAMP; ARLDVASEFRKKWNKWALSR-amide) has been determined using 1H and 13C, two-dimensional nuclear magnetic resonance (NMR) spectroscopy and, molecular modeling. PAMP is a peptide that has various physiological, functions, including its role as a proangiogenic factor in facilitating, tumor growth and its inhibitory effect on catecholamine secretion at, nicotinic receptors. The preferred conformation of PAMP was determined in, a helix-inducing trifluoroethanol and water (TFE/H2O) solution, and in a, membrane-mimetic sodium dodecylsulfate-d25 (SDS) micellar solution. The, secondary structure consists of an alpha-helix for residues Arg2 to Arg20, in TFE/H2O solution and an alpha-helix for residues Arg2 to Ala17 in SDS, solution. We postulate that the polar charged residues Arg2, Lys12, and, Arg20 are responsible for the initial interaction of the peptide with the, micelle, and that this is followed by the binding of the hydrophobic, residues Leu3, Val5, Phe9, Trp13, and Trp16 to the micellar core. The, three C-terminal amino acid residues adopt an extended structure in SDS, suggesting that they are important in receptor recognition and binding., This is supported by truncation studies done by Mahata et al., (Hypertension, 1998, Vol. 32, pp. 907-916), which show the importance of, the C-terminal in physiological activity. Furthermore, Belloni et al., (Hypertension, 1999, Vol. 33, pp. 1185-1189), and Martinez et al. (Cancer, Research, 2004, Vol. 64, pp. 6489-6494) suggested that the N-terminal was, also important in PAMP activity. However, no differences in conformational, preference of the N-terminal were observed between the two solvent, systems.

Disease

Known diseases associated with this structure: Alpha-methylacyl-CoA racemase deficiency OMIM:[604489], Glomerulocystic kidney disease with hyperuricemia and isosthenuria OMIM:[191845], Hyperuricemic nephropathy, familial juvenile OMIM:[191845], Medullary cystic kidney disease 2 OMIM:[191845]

About this Structure

2FLY is a Single protein structure of sequence from Homo sapiens with NH2 as ligand. Full crystallographic information is available from OCA.

Reference

NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth., Lucyk S, Taha H, Yamamoto H, Miskolzie M, Kotovych G, Biopolymers. 2006 Mar;81(4):295-308. PMID:16315141

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