6tnh

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Deoxyguanylosuccinate synthase (DgsS) quaternary structure with AMPPcP, dGMP, Asp, Magnesium at 2.21 Angstrom resolutionDeoxyguanylosuccinate synthase (DgsS) quaternary structure with AMPPcP, dGMP, Asp, Magnesium at 2.21 Angstrom resolution

Structural highlights

6tnh is a 2 chain structure with sequence from Vibrio phage phiVC8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.21Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PURZ_BPVC8 Involved in the synthesis of the atypical nucleotide dZTP (2-amino-2'-deoxyadenosine-5'-triphosphate) (PubMed:33926954). 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] [2]

Publication Abstract from PubMed

Cells have two purine pathways that synthesize adenine and guanine ribonucleotides from phosphoribose via inosylate. A chemical hybrid between adenine and guanine, 2-aminoadenine (Z), replaces adenine in the DNA of the cyanobacterial virus S-2L. We show that S-2L and Vibrio phage PhiVC8 encode a third purine pathway catalyzed by PurZ, a distant paralog of succinoadenylate synthase (PurA), the enzyme condensing aspartate and inosylate in the adenine pathway. PurZ condenses aspartate with deoxyguanylate into dSMP (N6-succino-2-amino-2'-deoxyadenylate), which undergoes defumarylation and phosphorylation to give dZTP (2-amino-2'-deoxyadenosine-5'-triphosphate), a substrate for the phage DNA polymerase. Crystallography and phylogenetics analyses indicate a close relationship between phage PurZ and archaeal PurA enzymes. Our work elucidates the biocatalytic innovation that remodeled a DNA building block beyond canonical molecular biology.

A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes.,Sleiman D, Garcia PS, Lagune M, Loc'h J, Haouz A, Taib N, Rothlisberger P, Gribaldo S, Marliere P, Kaminski PA Science. 2021 Apr 30;372(6541):516-520. doi: 10.1126/science.abe6494. PMID:33926955[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Zhou Y, Xu X, Wei Y, Cheng Y, Guo Y, Khudyakov I, Liu F, He P, Song Z, Li Z, Gao Y, Ang EL, Zhao H, Zhang Y, Zhao S. A widespread pathway for substitution of adenine by diaminopurine in phage genomes. Science. 2021 Apr 30;372(6541):512-516. doi: 10.1126/science.abe4882. PMID:33926954 doi:http://dx.doi.org/10.1126/science.abe4882
  2. Sleiman D, Garcia PS, Lagune M, Loc'h J, Haouz A, Taib N, Rothlisberger P, Gribaldo S, Marliere P, Kaminski PA. A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science. 2021 Apr 30;372(6541):516-520. doi: 10.1126/science.abe6494. PMID:33926955 doi:http://dx.doi.org/10.1126/science.abe6494
  3. Sleiman D, Garcia PS, Lagune M, Loc'h J, Haouz A, Taib N, Rothlisberger P, Gribaldo S, Marliere P, Kaminski PA. A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science. 2021 Apr 30;372(6541):516-520. doi: 10.1126/science.abe6494. PMID:33926955 doi:http://dx.doi.org/10.1126/science.abe6494

6tnh, resolution 2.21Å

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