7ODY

Cyanophage S-2L MazG-like pyrophosphohydrolase bound to dGDP and three catalytic Mn2+ ions per active site

Summary for 7ODY

• Entry DOI: 10.2210/pdb7ody/pdb
• Descriptor: MazG-like pyrophosphohydrolase (MazZ), 2'-DEOXYGUANOSINE-5'-DIPHOSPHATE, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: s-2l, mazg-like pyrophosphohydrolase, mazz, viral protein
• Biological source: Cyanophage S-2L
• Total number of polymer chains: 4
• Total formula weight: 50085.73

Authors

Czernecki, D.,Delarue, M. (deposition date: 2021-04-30, release date: 2021-09-01, Last modification date: 2024-06-19)

Primary citation

Czernecki, D.,Bonhomme, F.,Kaminski, P.A.,Delarue, M.
Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA.
Nat Commun, 12:4710-4710, 2021

PubMed Abstract: Cyanophage S-2L is known to profoundly alter the biophysical properties of its DNA by replacing all adenines (A) with 2-aminoadenines (Z), which still pair with thymines but with a triple hydrogen bond. It was recently demonstrated that a homologue of adenylosuccinate synthetase (PurZ) and a dATP triphosphohydrolase (DatZ) are two important pieces of the metabolism of 2-aminoadenine, participating in the synthesis of ZTGC-DNA. Here, we determine that S-2L PurZ can use either dATP or ATP as a source of energy, thereby also depleting the pool of nucleotides in dATP. Furthermore, we identify a conserved gene (mazZ) located between purZ and datZ genes in S-2L and related phage genomes. We show that it encodes a (d)GTP-specific diphosphohydrolase, thereby providing the substrate of PurZ in the 2-aminoadenine synthesis pathway. High-resolution crystal structures of S-2L PurZ and MazZ with their respective substrates provide a rationale for their specificities. The Z-cluster made of these three genes - datZ, mazZ and purZ - was expressed in E. coli, resulting in a successful incorporation of 2-aminoadenine in the bacterial chromosomal and plasmidic DNA. This work opens the possibility to study synthetic organisms containing ZTGC-DNA.

PubMed: 34354070
DOI: 10.1038/s41467-021-25064-x

Experimental method

X-RAY DIFFRACTION (1.43 Å)