7odx
From Proteopedia
Cyanophage S-2L Succinoaminodeoxyadenylate synthetase (PurZ) bound to dGMP and dATP as an energy donor
Structural highlights
FunctionPURZ_BPS2L Involved in the synthesis of the atypical nucleotide dZTP (2-amino-2'-deoxyadenosine-5'-triphosphate) (PubMed:33926955). Catalyzes the condensation of aspartate with deoxyguanylate into dSMP (N6-succino-2-amino-2'-deoxyadenylate), which undergoes defumarylation and phosphorylation respectively by host PurB and guanylate/nucleoside diphosphate kinases to give dZTP (PubMed:33926955). dZTP is integrated into the viral genome instead of adenine by the viral DNA polymerase. This Z-base probably completely replaces adenosine and forms a triple bond to the opposite T-base (PubMed:33926955). The resulting non-standard viral DNA is called Z-genome (PubMed:33926955). The chemically modified DNA is probably harder for the host bacteria to digest with nucleases or restriction enzymes (Probable).[HAMAP-Rule:MF_04166][1] Publication Abstract from PubMedCyanophage 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. Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA.,Czernecki D, Bonhomme F, Kaminski PA, Delarue M Nat Commun. 2021 Aug 5;12(1):4710. doi: 10.1038/s41467-021-25064-x. PMID:34354070[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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