8X4L

Crystal structure of the N132A mutant of DIMT1 from Pyrococcus horikoshii

Summary for 8X4L

• Entry DOI: 10.2210/pdb8x4l/pdb
• Descriptor: Probable ribosomal RNA small subunit methyltransferase A, ZINC ION, SULFITE ION, ... (8 entities in total)
• Functional Keywords: archaea, ksga/dimt1, rrna methyltransferase, sam, sah, sfg, transferase
• Biological source: Pyrococcus horikoshii OT3
• Total number of polymer chains: 2
• Total formula weight: 68441.40

Authors

Saha, S.,Kanaujia, S.P. (deposition date: 2023-11-15, release date: 2024-08-28, Last modification date: 2024-10-16)

Primary citation

Saha, S.,Kanaujia, S.P.
Structural and functional characterization of archaeal DIMT1 unveils distinct protein dynamics essential for efficient catalysis.
Structure, 32:1760-1775.e7, 2024

PubMed Abstract: Dimethyladenosine transferase 1 (DIMT1), an ortholog of bacterial KsgA is a conserved protein that assists in ribosome biogenesis by modifying two successive adenosine bases near the 3' end of small subunit (SSU) rRNA. Although KsgA/DIMT1 proteins have been characterized in bacteria and eukaryotes, they are yet unexplored in archaea. Also, their dynamics are not well understood. Here, we structurally and functionally characterized the apo and holo forms of archaeal DIMT1 from Pyrococcus horikoshii. Wild-type protein and mutants were analyzed to capture different transition states, including open, closed, and intermediate states. This study reports a unique inter-domain movement that is needed for substrate (RNA) positioning in the catalytic pocket, and is only observed in the presence of the cognate cofactors S-adenosyl-L-methionine (SAM) or S-adenosyl-L-homocysteine (SAH). The binding of the inhibitor sinefungine, an analog of SAM or SAH, to archaeal DIMT1 blocks the catalytic pocket and renders the enzyme inactive.

PubMed: 39146930
DOI: 10.1016/j.str.2024.07.013

Experimental method

X-RAY DIFFRACTION (2.6 Å)