9C3S

Crystal structure of DNA N6-Adenine Methyltransferase M.BceJIV from Burkholderia cenocepacia in complex with duplex DNA substrate containing GTATAC as recognition sequence

Summary for 9C3S

• Entry DOI: 10.2210/pdb9c3s/pdb
• Related: 8URK
• Related PRD ID: PRD_900003
• Descriptor: Methyltransferase, DNA1, DNA2, ... (6 entities in total)
• Functional Keywords: dna n6-adenine methyltransferase, m.bcejiv, burkholderia cenocepacia, dna binding protein
• Biological source: Burkholderia cenocepacia; More
• Total number of polymer chains: 12
• Total formula weight: 162064.92

Authors

Kottur, J.,Quintana-Feliciano, R.,Aggarwal, A.K. (deposition date: 2024-06-02, release date: 2024-09-11, Last modification date: 2024-09-18)

Primary citation

Quintana-Feliciano, R.,Kottur, J.,Ni, M.,Ghosh, R.,Salas-Estrada, L.,Ahlsen, G.,Rechkoblit, O.,Shapiro, L.,Filizola, M.,Fang, G.,Aggarwal, A.K.
Burkholderia cenocepacia epigenetic regulator M.BceJIV simultaneously engages two DNA recognition sequences for methylation.
Nat Commun, 15:7839-7839, 2024

PubMed Abstract: Burkholderia cenocepacia is an opportunistic and infective bacterium containing an orphan DNA methyltransferase called M.BceJIV with roles in regulating gene expression and motility of the bacterium. M.BceJIV recognizes a GTWWAC motif (where W can be an adenine or a thymine) and methylates N6 of the adenine at the fifth base position. Here, we present crystal structures of M.BceJIV/DNA/sinefungin ternary complex and allied biochemical, computational, and thermodynamic analyses. Remarkably, the structures show not one, but two DNA substrates bound to the M.BceJIV dimer, with each monomer contributing to the recognition of two recognition sequences. We also show that methylation at the two recognition sequences occurs independently, and that the GTWWAC motifs are enriched in intergenic regions in the genomes of B. cenocepacia strains. We further computationally assess the interactions underlying the affinities of different ligands (SAM, SAH, and sinefungin) for M.BceJIV, as a step towards developing selective inhibitors for limiting B. cenocepacia infection.

PubMed: 39244607
DOI: 10.1038/s41467-024-52130-x

Experimental method

X-RAY DIFFRACTION (2.16 Å)