7EQF

Crystal Structure of a Transcription Factor in complex with Ligand

7EQF の概要

• エントリーDOI: 10.2210/pdb7eqf/pdb
• 関連するPDBエントリー: 7EQE
• 分子名称: TetR/AcrR family transcriptional regulator, (6~{R})-3-methyl-8-[(2~{S},4~{R},5~{S},6~{R})-6-methyl-5-[(2~{S},4~{R},5~{R},6~{R})-6-methyl-4-[(2~{S},5~{S},6~{S})-6-methyl-5-[(2~{S},4~{R},5~{S},6~{R})-6-methyl-5-[(2~{S},4~{S},5~{S},6~{R})-6-methyl-4-[(2~{S},5~{S},6~{S})-6-methyl-5-oxidanyl-oxan-2-yl]oxy-5-oxidanyl-oxan-2-yl]oxy-4-oxidanyl-oxan-2-yl]oxy-oxan-2-yl]oxy-5-oxidanyl-oxan-2-yl]oxy-4-oxidanyl-oxan-2-yl]oxy-1,6,11-tris(oxidanyl)-5,6-dihydrobenzo[a]anthracene-7,12-dione (2 entities in total)
• 機能のキーワード: transcription factor, transcription
• 由来する生物種: Streptomyces griseoluteus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 92603.19

構造登録者

Uehara, S.,Tsugita, A.,Matsui, T.,Yokoyama, T.,Ostash, I.,Ostash, B.,Tanaka, Y. (登録日: 2021-05-01, 公開日: 2022-04-27, 最終更新日: 2023-11-29)

主引用文献

Tsugita, A.,Uehara, S.,Matsui, T.,Yokoyama, T.,Ostash, I.,Deneka, M.,Yalamanchili, S.,Bennett, C.S.,Tanaka, Y.,Ostash, B.
The carbohydrate tail of landomycin A is responsible for its interaction with the repressor protein LanK.
Febs J., 289:6038-6057, 2022

PubMed Abstract: Landomycin A (LaA) is the largest member of the landomycin group of angucyclic polyketides. Its unusual structure and strong anticancer properties have attracted great interest from chemists and biologists alike. This, in particular, has led to a detailed picture of LaA biosynthesis in Streptomyces cyanogenus S136, the only known LaA producer. LanK is a TetR family repressor protein that limits the export of landomycins from S136 cells until significant amounts of the final product, LaA, have accumulated. Landomycins carrying three or more carbohydrate units in their glycosidic chain are effector molecules for LanK. Yet, the exact mechanism that LanK uses to distinguish the final product, LaA, from intermediate landomycins and sense accumulation of LaA was not known. Here, we report crystal structures of LanK, alone and in complex with LaA, and bioassays of LanK's interaction with synthetic carbohydrate chains of LaA (hexasaccharide) and LaE (trisaccharide). Our data collectively suggest that the carbohydrate moieties are the sole determinants of the interaction of the landomycins with LanK, triggering the latter's dissociation from the lanK-lanJ intergenic region via structure conversion of the helices in the C-terminal ligand-binding domain. Analysis of the available literature suggests that LanK represents an unprecedented type of TetR family repressor that recognises the carbohydrate portion of a natural product, and not an aglycon, as it is the case, for example, with the SimR repressor involved in simocyclinone biosynthesis.

PubMed: 35429224
DOI: 10.1111/febs.16460

実験手法

X-RAY DIFFRACTION (2.91 Å)