7ROA
Crystal structure of EntV136 from Enterococcus faecalis
Summary for 7ROA
Entry DOI | 10.2210/pdb7roa/pdb |
Descriptor | EntV (2 entities in total) |
Functional Keywords | all alpha protein, antifungal, structural genomics, csgid, center for structural genomics of infectious diseases, niaid, national institute of allergy and infectious diseases, antifungal protein |
Biological source | Enterococcus faecalis OG1RF (Streptococcus faecalis) |
Total number of polymer chains | 1 |
Total formula weight | 14938.54 |
Authors | Stogios, P.J.,Evdokimova, E.,Kim, Y.,Garsin, D.,Savchenko, A.,Joachimiak, A.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2021-07-30, release date: 2022-10-12, Last modification date: 2023-01-25) |
Primary citation | Cruz, M.R.,Cristy, S.,Guha, S.,De Cesare, G.B.,Evdokimova, E.,Sanchez, H.,Borek, D.,Miramon, P.,Yano, J.,Fidel Jr., P.L.,Savchenko, A.,Andes, D.R.,Stogios, P.J.,Lorenz, M.C.,Garsin, D.A. Structural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections. Nat Commun, 13:6047-6047, 2022 Cited by PubMed Abstract: Fungal pathogens are a continuing challenge due to few effective antifungals and a rise in resistance. In previous work, we described the inhibition of Candida albicans virulence following exposure to the 68 amino acid bacteriocin, EntV, secreted by Enterococcus faecalis. Here, to optimize EntV as a potential therapeutic and better understand its antifungal features, an X-ray structure is obtained. The structure consists of six alpha helices enclosing a seventh 16 amino acid helix (α7). The individual helices are tested for antifungal activity using in vitro and nematode infection assays. Interestingly, α7 retains antifungal, but not antibacterial activity and is also effective against Candida auris and Cryptococcus neoformans. Further reduction of α7 to 12 amino acids retains full antifungal activity, and excellent efficacy is observed in rodent models of C. albicans oropharyngeal, systemic, and venous catheter infections. Together, these results showcase EntV-derived peptides as promising candidates for antifungal therapeutic development. PubMed: 36229448DOI: 10.1038/s41467-022-33613-1 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
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