Structural highlights
Function
[CMGA_BOVIN] Pancreastatin strongly inhibits glucose induced insulin release from the pancreas. Chromostatin completely inhibits catecholamine release from chromaffin cells. Chromacin has antibacterial activity against M.luteus. Not active against E.coli. Catestatin inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Vasostatin-1 has antibacterial activity against Gram-positive bacteria M.luteus, B.megaterium. Not active against Gram-positive bacteria B.cereus, B.subtilis, S.pyogenes, M.fortuitum, S.aureus and L.monocytogenes and against Gram-negative bacteria E.coli, E.cloacae, S.typhimurium, K.pneumoniae and P.aeruginosa. Possesses antifungal activity against N.crassa, A.fumigatus, A.brassicicola, N.hematococca, F.culmorum and F.oxyporum and against the yeast S.cerevisiae and C.albicans. Inactive against T.mentagrophytes.
Publication Abstract from PubMed
Previous modeling (PDB 1cfk) of the catecholamine release-inhibitory "catestatin" region of chromogranin A (CgA) suggested a beta-strand/loop/beta-strand active conformation, displaying an electropositive Arg-rich loop (R(351)AR(353)GYGFR(358)). To explore this possibility, we studied NMR structures of linear and cyclic synthetic catestatin, bovine (bCgA(344-364)) or human (hCgA(352-372)). By 2-D (1)H-NMR, the structure of linear catestatin (hCgA(352-372)) exhibited the NOE pattern of a coiled loop (PDB 1lv4). We then constrained the structure, cyclizing the putative Arg-rich loop connecting the beta-strands: cyclic bCgA(350-362) ([C(0)]F(350)RARGYGFRGPGL(362)[C(+14)]). Favored conformations of cyclic bCgA(350-362) were determined by (1)H-NMR and (13)C-NMR spectroscopy. Cyclic bCgA(350-362) conformers (PDB 1n2y) adopted a "twisted-loop" conformation. Alignment between the homology model and the cyclic NMR structure showed that, while portions of the NMR structure's mid-molecule and carboxy-terminus were congruent with the homology model (RMSD, 1.61-1.91 A), the amino-terminal "twisted loop" coiled inward and away from the model (RMSD, 3.36 A). Constrained cyclic bCgA(350-362) did not exert nicotinic cholinergic antagonist activity (IC(50)>10 microM), when compared to full-length linear (IC(50) approximately 0.42-0.56 microM), or cyclic (IC(50) approximately 0.74 microM) catestatin. Thus, loss of activity in the small, constrained peptide did not result from either [Cys]-extension or cyclization, per se. While linear catestatin displays coiled character, a small cyclic derivative lost biological activity, perhaps because its amino-terminal domain deviated sharply from the predicted active conformation. These results refine the relationship between structure and function in catestatin, and suggest goals in future peptidomimetic syntheses, in particular attempts to constrain the correct amino-terminal shape for biological activity.
Conformational preferences and activities of peptides from the catecholamine release-inhibitory (catestatin) region of chromogranin A.,Preece NE, Nguyen M, Mahata M, Mahata SK, Mahapatra NR, Tsigelny I, O'Connor DT Regul Pept. 2004 Apr 15;118(1-2):75-87. PMID:14759560[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Preece NE, Nguyen M, Mahata M, Mahata SK, Mahapatra NR, Tsigelny I, O'Connor DT. Conformational preferences and activities of peptides from the catecholamine release-inhibitory (catestatin) region of chromogranin A. Regul Pept. 2004 Apr 15;118(1-2):75-87. PMID:14759560 doi:http://dx.doi.org/10.1016/j.regpep.2003.10.035
