BACKGROUND: The protegrins are a family of arginine- and cysteine-rich cationic peptides found in porcine leukocytes that exhibit a broad range of antimicrobial and antiviral activities. They are composed of 16-18 amino-acid residues including four cysteines, which form two disulfide linkages. To begin to understand the mechanism of action of these peptides, we set out to determine the structure of protegrin-1 (PG-1). RESULTS: We used two-dimensional homonuclear nuclear magnetic resonance spectroscopy to study the conformation of both natural and synthetic PG-1 under several conditions. A refined three-dimensional structure of synthetic PG-1 is presented. CONCLUSIONS: Both synthetic and natural protegrin-1 form a well-defined structure in solution composed primarily of a two-stranded antiparallel beta sheet, with strands connected by a beta turn. The structure of PG-1 suggests ways in which the peptide may interact with itself or other molecules to form the membrane pores and the large membrane-associated assemblages observed in protegrin-treated, gram-negative bacteria.
BACKGROUND: The protegrins are a family of arginine- and cysteine-rich cationic peptides found in porcine leukocytes that exhibit a broad range of antimicrobial and antiviral activities. They are composed of 16-18 amino-acid residues including four cysteines, which form two disulfide linkages. To begin to understand the mechanism of action of these peptides, we set out to determine the structure of protegrin-1 (PG-1). RESULTS: We used two-dimensional homonuclear nuclear magnetic resonance spectroscopy to study the conformation of both natural and synthetic PG-1 under several conditions. A refined three-dimensional structure of synthetic PG-1 is presented. CONCLUSIONS: Both synthetic and natural protegrin-1 form a well-defined structure in solution composed primarily of a two-stranded antiparallel beta sheet, with strands connected by a beta turn. The structure of PG-1 suggests ways in which the peptide may interact with itself or other molecules to form the membrane pores and the large membrane-associated assemblages observed in protegrin-treated, gram-negative bacteria.
Authors: David Gidalevitz; Yuji Ishitsuka; Adrian S Muresan; Oleg Konovalov; Alan J Waring; Robert I Lehrer; Ka Yee C Lee Journal: Proc Natl Acad Sci U S A Date: 2003-05-08 Impact factor: 11.205
Authors: D A Steinberg; M A Hurst; C A Fujii; A H Kung; J F Ho; F C Cheng; D J Loury; J C Fiddes Journal: Antimicrob Agents Chemother Date: 1997-08 Impact factor: 5.191
Authors: Kshitij Gupta; Hyunbum Jang; Kevin Harlen; Anu Puri; Ruth Nussinov; Joel P Schneider; Robert Blumenthal Journal: Biophys J Date: 2013-11-05 Impact factor: 4.033