6SRN

Structural basis for control of antibiotic production by bacterial hormones

6SRN の概要

• エントリーDOI: 10.2210/pdb6srn/pdb
• 分子名称: TetR family transcriptional regulator, 4-(Hydroxymethyl)-2-propylfuran-3-carboxylic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: antibiotic, streptomyces, tetr-family transcriptional regulator, signalling, microbial natural product
• 由来する生物種: Streptomyces coelicolor
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24301.55

構造登録者

Fulop, V. (登録日: 2019-09-05, 公開日: 2020-09-30, 最終更新日: 2024-05-15)

主引用文献

Zhou, S.,Bhukya, H.,Malet, N.,Harrison, P.J.,Rea, D.,Belousoff, M.J.,Venugopal, H.,Sydor, P.K.,Styles, K.M.,Song, L.,Cryle, M.J.,Alkhalaf, L.M.,Fulop, V.,Challis, G.L.,Corre, C.
Molecular basis for control of antibiotic production by a bacterial hormone.
Nature, 590:463-467, 2021

PubMed Abstract: Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR. Here we report the X-ray crystal structure of an MmfR-AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR-operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.

PubMed: 33536618
DOI: 10.1038/s41586-021-03195-x

実験手法

X-RAY DIFFRACTION (1.5 Å)