PDBsum entry 6azh

Transcription

PDB id: 6azh

Contents

Protein chains

189 a.a.

Waters ×395

PDB id:

6azh

Name:

Transcription

Title:

Clostridium perfringens putative fatty acid metabolism regulator

Structure:

Tetr family transcriptional regulator. Chain: a, b. Engineered: yes

Source:

Clostridium perfringens. Organism_taxid: 1502. Gene: bxt94_00180. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.75Å R-factor: 0.198 R-free: 0.225

Authors:

W.G.William,M.R.Redinbo

Key ref:

M.S.Little et al. (2018). Structural basis for the regulation of β-glucuronidase expression by human gut Enterobacteriaceae. Proc Natl Acad Sci U S A, 115, E152. PubMed id: 29269393

Date:

11-Sep-17 Release date: 20-Dec-17

Protein chains

A0A1U9V3V3  () -

Proc Natl Acad Sci U S A 115:E152 (2018)

PubMed id: 29269393

Structural basis for the regulation of β-glucuronidase expression by human gut Enterobacteriaceae.

M.S.Little, S.J.Pellock, W.G.Walton, A.Tripathy, M.R.Redinbo.

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 inEscherichia,Salmonella,Klebsiella,Shigella, andYersiniaopportunistic 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 fromEscherichia coliandSalmonella entericain complexes with a glucuronide ligand. The GusR-specific DNA operator site in the regulatory region of theE. coliGUS 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 transferE. coliGusR's preferential DNA and glucuronide binding affinity toS. entericaGusR. 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.