8EV5

NlpC B3 covalently bound with E64 inhibitor fragment

8EV5 の概要

• エントリーDOI: 10.2210/pdb8ev5/pdb
• 分子名称: Clan CA, family C40, NlpC/P60 superfamily cysteine peptidase, N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: nlpc, p60, chap, nlpc/p60, cysteine protease, inhibitor, e64, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Trichomonas vaginalis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13670.52

構造登録者

Barnett, M.J.,Goldstone, D.C. (登録日: 2022-10-19, 公開日: 2023-09-06, 最終更新日: 2024-11-13)

主引用文献

Barnett, M.J.,Pinheiro, J.,Keown, J.R.,Biboy, J.,Gray, J.,Lucinescu, I.W.,Vollmer, W.,Hirt, R.P.,Simoes-Barbosa, A.,Goldstone, D.C.
NlpC/P60 peptidoglycan hydrolases of Trichomonas vaginalis have complementary activities that empower the protozoan to control host-protective lactobacilli.
Plos Pathog., 19:e1011563-e1011563, 2023

PubMed Abstract: Trichomonas vaginalis is a human protozoan parasite that causes trichomoniasis, a prevalent sexually transmitted infection. Trichomoniasis is accompanied by a shift to a dysbiotic vaginal microbiome that is depleted of lactobacilli. Studies on co-cultures have shown that vaginal bacteria in eubiosis (e.g. Lactobacillus gasseri) have antagonistic effects on T. vaginalis pathogenesis, suggesting that the parasite might benefit from shaping the microbiome to dysbiosis (e.g. Gardnerella vaginalis among other anaerobes). We have recently shown that T. vaginalis has acquired NlpC/P60 genes from bacteria, expanding them to a repertoire of nine TvNlpC genes in two distinct clans, and that TvNlpCs of clan A are active against bacterial peptidoglycan. Here, we expand this characterization to TvNlpCs of clan B. In this study, we show that the clan organisation of NlpC/P60 genes is a feature of other species of Trichomonas, and that Histomonas meleagridis has sequences related to one clan. We characterized the 3D structure of TvNlpC_B3 alone and with the inhibitor E64 bound, probing the active site of these enzymes for the first time. Lastly, we demonstrated that TvNlpC_B3 and TvNlpC_B5 have complementary activities with the previously described TvNlpCs of clan A and that exogenous expression of these enzymes empower this mucosal parasite to take over populations of vaginal lactobacilli in mixed cultures. TvNlpC_B3 helps control populations of L. gasseri, but not of G. vaginalis, which action is partially inhibited by E64. This study is one of the first to show how enzymes produced by a mucosal protozoan parasite may contribute to a shift on the status of a microbiome, helping explain the link between trichomoniasis and vaginal dysbiosis. Further understanding of this process might have significant implications for treatments in the future.

PubMed: 37585473
DOI: 10.1371/journal.ppat.1011563

実験手法

X-RAY DIFFRACTION (1.65 Å)