6RSF
NMR structure of pleurocidin KR in SDS micelles
Summary for 6RSF
| Entry DOI | 10.2210/pdb6rsf/pdb |
| NMR Information | BMRB: 34404 |
| Descriptor | Pleurocidin (1 entity in total) |
| Functional Keywords | amp, pleurocidin analogue, winter flounder, sds micelles, sequence optimization, antimicrobial protein |
| Biological source | Pseudopleuronectes americanus (Winter flounder) |
| Total number of polymer chains | 1 |
| Total formula weight | 2830.24 |
| Authors | Manzo, G.,Mason, A.J. (deposition date: 2019-05-21, release date: 2020-12-09, Last modification date: 2024-06-19) |
| Primary citation | Manzo, G.,Hind, C.K.,Ferguson, P.M.,Amison, R.T.,Hodgson-Casson, A.C.,Ciazynska, K.A.,Weller, B.J.,Clarke, M.,Lam, C.,Man, R.C.H.,Shaughnessy, B.G.O.,Clifford, M.,Bui, T.T.,Drake, A.F.,Atkinson, R.A.,Lam, J.K.W.,Pitchford, S.C.,Page, C.P.,Phoenix, D.A.,Lorenz, C.D.,Sutton, J.M.,Mason, A.J. A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy. Commun Biol, 3:697-697, 2020 Cited by PubMed Abstract: Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15 mg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs. PubMed: 33247193DOI: 10.1038/s42003-020-01420-3 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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