1RKK

POLYPHEMUSIN I NMR SOLUTION STRUCTURE

Summary for 1RKK

• Entry DOI: 10.2210/pdb1rkk/pdb
• NMR Information: BMRB: 6020
• Descriptor: POLYPHEMUSIN I (1 entity in total)
• Functional Keywords: polyphemusin, beta hairpin, disulfide bridge, anti-microbial peptide, antimicrobial peptide
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 2464.02

Authors

Powers, J.P.S.,Rozek, A.,Hancock, R.E.W. (deposition date: 2003-11-21, release date: 2004-08-31, Last modification date: 2024-11-13)

Primary citation

Powers, J.P.S.,Rozek, A.,Hancock, R.E.W.
Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin I.
BIOCHIM.BIOPHYS.ACTA, 1698:239-250, 2004

PubMed Abstract: The solution structure of polyphemusin I was determined using (1)H-NMR spectroscopy. Polyphemusin I was found to be an amphipathic, beta-hairpin connected by a type I' beta-turn. The 17 low-energy structures aligned very well over the beta-sheet region while both termini were poorly defined due in part to a hinge-like region centred in the molecule about arginine residues 6 and 16. Conversely, a linear analogue, PM1-S, with all cysteines simultaneously replaced with serine was found to be dynamic in nature, and a lack of medium and long-range NOEs indicated that this molecule displayed no favoured conformation. Circular dichroism (CD) spectroscopy confirmed that in solution, 50% trifluoroethanol (TFE) and in the presence of liposomes, PM1-S remained unstructured. The antimicrobial activity of PM1-S was found to be 4- to 16-fold less than that of polyphemusin I and corresponded with a 4-fold reduction in bacterial membrane depolarization. Both peptides were able to associate with lipid bilayers in a similar fashion; however, PM1-S was completely unable to translocate model membranes while polyphemusin I retained this activity. It was concluded that the disulfide-constrained, beta-sheet structure of polyphemusin I is required for maximum antimicrobial activity. Disruption of this structure results in reduced antimicrobial activity and completely abolishes membrane translocation indicating that the linear PM1-S acts through a different antimicrobial mechanism.

PubMed: 15134657

Experimental method

SOLUTION NMR