1t54
From Proteopedia
Antibiotic Activity and Structural Analysis of a Scorpion-derived Antimicrobial peptide IsCT and Its Analogs
Overview
IsCT is a non-cell-selective antimicrobial peptide isolated from the scorpion Opisthacanthus madagascariensis that has potent cytolytic activity against both mammalian and bacterial cells. To investigate the structure-activity relationships of IsCT and to design novel peptide antibiotics with bacterial cell selectivity, we synthesized several analogs of IsCT and determined their three-dimensional structures in solution by 2D-NMR spectroscopy. IsCT has a linear alpha-helical structure from Gly3 to Phe13, and [K7]-IsCT has a linear alpha-helical structure from Leu2 to Phe13. [K7, P8, K11]-IsCT, which has a bend in its middle region, exhibited the highest antibacterial activity without hemolytic activity, suggesting that its proline-induced bend is an important determinant of this selectivity. Tryptophan fluorescence showed that the high selectivity of [K7, P8, K11]-IsCT toward bacterial cells is closely correlated with its highly selective interaction with negatively charged phospholipids. Its potent activity against antibiotic-resistant bacteria suggests that [K7, P8, K11]-IsCT may serve as a promising lead candidate in the development of new peptide antibiotics.
About this Structure
1T54 is a Single protein structure of sequence from Opisthacanthus madagascariensis. Full crystallographic information is available from OCA.
Reference
Antibiotic activity and structural analysis of the scorpion-derived antimicrobial peptide IsCT and its analogs., Lee K, Shin SY, Kim K, Lim SS, Hahm KS, Kim Y, Biochem Biophys Res Commun. 2004 Oct 15;323(2):712-9. PMID:15369808 Page seeded by OCA on Sat May 3 09:32:17 2008
