7EI3

Crystal structure of MasL, a thiolase from Massilia sp. YMA4

7EI3 の概要

• エントリーDOI: 10.2210/pdb7ei3/pdb
• 分子名称: Acetyl-CoA C-acyltransferase (2 entities in total)
• 機能のキーワード: acetyl-coa acetyltransferase, transferase
• 由来する生物種: [Empedobacter] haloabium
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 170429.33

構造登録者

Lin, C.C.,Huang, K.F.,Yang, Y.L. (登録日: 2021-03-30, 公開日: 2022-04-06, 最終更新日: 2023-11-29)

主引用文献

Lin, C.C.,Hoo, S.Y.,Ma, L.T.,Lin, C.,Huang, K.F.,Ho, Y.N.,Sun, C.H.,Lee, H.J.,Chen, P.Y.,Shu, L.J.,Wang, B.W.,Hsu, W.C.,Ko, T.P.,Yang, Y.L.
Integrated omics approach to unveil antifungal bacterial polyynes as acetyl-CoA acetyltransferase inhibitors.
Commun Biol, 5:454-454, 2022

PubMed Abstract: Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited the cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for developing antifungal agents.

PubMed: 35551233
DOI: 10.1038/s42003-022-03409-6

実験手法

X-RAY DIFFRACTION (1.78 Å)