7ROA

Crystal structure of EntV136 from Enterococcus faecalis

7ROA の概要

• エントリーDOI: 10.2210/pdb7roa/pdb
• 分子名称: EntV (2 entities in total)
• 機能のキーワード: all alpha protein, antifungal, structural genomics, csgid, center for structural genomics of infectious diseases, niaid, national institute of allergy and infectious diseases, antifungal protein
• 由来する生物種: Enterococcus faecalis OG1RF (Streptococcus faecalis)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14938.54

構造登録者

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) (登録日: 2021-07-30, 公開日: 2022-10-12, 最終更新日: 2024-11-20)

主引用文献

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

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: 36229448
DOI: 10.1038/s41467-022-33613-1

実験手法

X-RAY DIFFRACTION (1.82 Å)