5gwg
From Proteopedia
Solution structure of rattusin
Structural highlights
FunctionDFAL1_RAT Intestinal defense peptide (PubMed:23380721, PubMed:28345637). Has potent antibacterial activity against Gram-negative bacteria E.coli O157:H7, S.typhimurium DT104, and K.pneumoniae; and against Gram-positive bacteria S.aureus, methicillin-resistant S.aureus and L.monocytogenes (PubMed:23380721, PubMed:28345637). Remains active in the presence of NaCl and Mg(2+) (PubMed:23380721). Probably functions by disrupting bacterial membrane integrity (PubMed:28345637). However, does not show cytotoxic activity towards human intestinal cells (PubMed:23380721).[1] [2] Publication Abstract from PubMedDefensin peptides are essential for innate immunity in humans and other living systems, as they provide protection against infectious pathogens and regulate the immune response. Here, we report the solution structure of rattusin (RTSN), an alpha-defensin-related peptide, which revealed a novel C2-symmetric disulfide-linked dimeric structure. RTSN was synthesized by solid-phase peptide synthesis (SPPS) and refolded by air oxidation in vitro. Dimerization of the refolded RTSN (r-RTSN) resulted from five intermolecular disulfide (SS) bond exchanges formed by ten cysteines within two protomer chains. The SS bond pairings of r-RTSN were determined by mass analysis of peptide fragments cleaved by trypsin digestion. In addition to mass analysis, nuclear magnetic resonance (NMR) experiments for a C15S mutant and r-RTSN confirmed that the intermolecular SS bond structure of r-RTSN showed an I-V', II-IV', III-III', IV-II', V-I' arrangement. The overall structure of r-RTSN exhibited a cylindrical array, similar to that of beta-sandwich folds, with a highly basic surface. Furthermore, fluorescence spectroscopy results suggest that r-RTSN exerts bactericidal activity by damaging membrane integrity. Collectively, these results provide a novel structural scaffold for designing highly potent peptide-based antibiotics suitable for use under various physiological conditions. Rattusin structure reveals a novel defensin scaffold formed by intermolecular disulfide exchanges.,Min HJ, Yun H, Ji S, Rajasekaran G, Kim JI, Kim JS, Shin SY, Lee CW Sci Rep. 2017 Mar 27;7:45282. doi: 10.1038/srep45282. PMID:28345637[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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