8Z2O

Crystal structure of 5-N-alpha-glycinylthymidine (N-alpha-GlyT) FAD-dependent lyase gp47/NGTO from Pseudomonads phage PaMx11

Summary for 8Z2O

• Entry DOI: 10.2210/pdb8z2o/pdb
• Descriptor: Flavin-dependent lyase, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, GLYCEROL, ... (6 entities in total)
• Functional Keywords: dna hypermodification, phage, 5-n-apha-glycinylthymidine, n-alpha-glyt, pseudomonads pamx11, oxidoreductase, fad
• Biological source: Pseudomonas phage PaMx11
• Total number of polymer chains: 1
• Total formula weight: 32226.37

Authors

Wen, Y.,Guo, W.T.,Wu, B.X. (deposition date: 2024-04-13, release date: 2024-10-02, Last modification date: 2024-10-30)

Primary citation

Wen, Y.,Guo, W.,Meng, C.,Yang, J.,Xu, S.,Chen, H.,Gan, J.,Wu, B.
Structural insights into the biosynthetic mechanism of N alpha-GlyT and 5-NmdU hypermodifications of DNA.
Nucleic Acids Res., 52:11083-11097, 2024

PubMed Abstract: DNA hypermodifications are effective weapons for phages to cope with the defense system of bacteria. The biogenesis of DNA hypermodification in phages involves multiple steps, from the modified deoxynucleotide monophosphates to the final hypermodification on the DNA chains. PseudomonasPaMx11 gp46 and gp47 encode the enzymes for sequentially converting 5-phosphomethyl-2'-deoxyuridine to 5-Nα-glycinylthymidine and 5-aminomethyl-2'-deoxyuridine. Here, we have determined the crystal structures of gp46 and gp47 in their apo and double-stranded DNA (dsDNA)-bound forms. We uncovered their dsDNA recognition properties and identified the critical residues for the catalytic reactions. Combined with in vitro biochemical studies, we proposed a plausible reaction scheme for gp46 and gp47 in converting these DNA hypermodifications. Our studies will provide the structural basis for future bioengineering of the synthetic pathway of hypermodification and identifying new modifications in mammals by enzyme-assisted sequencing methods.

PubMed: 39268585
DOI: 10.1093/nar/gkae784

Experimental method

X-RAY DIFFRACTION (2.3 Å)