9VG2

Crystal structure of C. difficile HsmR with DNA bound

Summary for 9VG2

• Entry DOI: 10.2210/pdb9vg2/pdb
• Related: 8ZDE
• Descriptor: MarR-family transcriptional regulator, DNA (5'-D(*AP*TP*TP*AP*GP*TP*TP*TP*GP*TP*AP*TP*GP*CP*AP*AP*AP*CP*CP*AP*TP*T)-3'), PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: marr, transcription
• Biological source: Clostridioides difficile; More
• Total number of polymer chains: 4
• Total formula weight: 52273.15

Authors

Park, S.Y. (deposition date: 2025-06-12, release date: 2026-05-13)

Primary citation

Rho, S.,Kwon, N.,Park, S.
DNA-bound structure of Clostridioides difficile heme-sensing HsmR gives insight on how the unique dimer mode governs DNA specificity in MarR transcriptional regulators.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: Clostridioides difficile is a pathogenic bacterium responsible for illnesses ranging from diarrhea to life-threatening colitis and has emerged as a significant public health concern due to its resistance to antibiotics. During its infection, intestinal bleeding causes lysis of the red blood cells releasing heme, a toxic oxidant for the bacterium. To counteract, HsmR of the MarR family transcriptional regulator senses the heme and induces the expression of HsmA to sequester the heme. The structure of HsmR in complex with its cognate pseudo-palindromic DNA illustrates that the lysine and arginine of the winged helix-turn-helix motif undergo conformational changes to accommodate the DNA, and to interact with specific DNA bases. However, conservation of these residues in half of 14 or so C. difficile MarRs within its genome raises a question on how specificity between MarR and DNA is achieved. Comparisons of various C. difficile MarR structures suggest that they probably have acquired DNA selectivity by the slightly different dimeric mode mediated by mutual interaction between the first helices of each HsmR subunit. The unique HsmR dimer mode allows symmetric recognition toward its own cognate DNA, and heme binding would happen in concert with reorientation of these helices in turn affecting DNA binding.

PubMed: 41123208
DOI: 10.1093/nar/gkaf1032

Experimental method

X-RAY DIFFRACTION (2.2 Å)