6AYH

Salmonella enterica GusR

6AYH の概要

• エントリーDOI: 10.2210/pdb6ayh/pdb
• 分子名称: TetR family transcriptional regulator, GLYCEROL, 4-nitrophenyl beta-D-glucopyranosiduronic acid, ... (4 entities in total)
• 機能のキーワード: transcriptional repressor protein, glucuronide binding protein, dna binding protein, transcription
• 由来する生物種: Salmonella choleraesuis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22959.83

構造登録者

Little, M.S.,Pellock, S.J. (登録日: 2017-09-08, 公開日: 2017-12-20, 最終更新日: 2024-11-06)

主引用文献

Little, M.S.,Pellock, S.J.,Walton, W.G.,Tripathy, A.,Redinbo, M.R.
Structural basis for the regulation of beta-glucuronidase expression by human gut Enterobacteriaceae.
Proc. Natl. Acad. Sci. U.S.A., 115:E152-E161, 2018

PubMed Abstract: The gut microbiota harbor diverse β-glucuronidase (GUS) enzymes that liberate glucuronic acid (GlcA) sugars from small-molecule conjugates and complex carbohydrates. However, only the Enterobacteriaceae family of human gut-associated Proteobacteria maintain a GUS operon under the transcriptional control of a glucuronide repressor, GusR. Despite its potential importance in , , , , and opportunistic pathogens, the structure of GusR has not been examined. Here, we explore the molecular basis for GusR-mediated regulation of GUS expression in response to small-molecule glucuronides. Presented are 2.1-Å-resolution crystal structures of GusRs from and in complexes with a glucuronide ligand. The GusR-specific DNA operator site in the regulatory region of the GUS operon is identified, and structure-guided GusR mutants pinpoint the residues essential for DNA binding and glucuronide recognition. Interestingly, the endobiotic estradiol-17-glucuronide and the xenobiotic indomethacin-acyl-glucuronide are found to exhibit markedly differential binding to these GusR orthologs. Using structure-guided mutations, we are able to transfer GusR's preferential DNA and glucuronide binding affinity to GusR. Structures of putative GusR orthologs from GUS-encoding Firmicutes species also reveal functionally unique features of the Enterobacteriaceae GusRs. Finally, dominant-negative GusR variants are validated in cell-based studies. These data provide a molecular framework toward understanding the control of glucuronide utilization by opportunistic pathogens in the human gut.

PubMed: 29269393
DOI: 10.1073/pnas.1716241115

実験手法

X-RAY DIFFRACTION (2.05 Å)