Structural highlights
8tg3 is a 1 chain structure with sequence from Aeropyrum pernix. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 1.47Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KPTA_AERPE Removes the 2'-phosphate from RNA via an intermediate in which the phosphate is ADP-ribosylated by NAD followed by a presumed transesterification to release the RNA and generate ADP-ribose 1-2-cyclic phosphate (APPR>P). May function as an ADP-ribosylase (By similarity).
Publication Abstract from PubMed
Tpt1 is an essential agent of fungal and plant tRNA splicing that removes an internal RNA 2'-phosphate generated by tRNA ligase. Tpt1 also removes the 2'-phosphouridine mark installed by Ark1 kinase in the V-loop of archaeal tRNAs. Tpt1 performs a two-step reaction in which the 2'-PO(4) attacks NAD(+) to form an RNA-2'-phospho-(ADP-ribose) intermediate, and transesterification of the ADP-ribose O2 to the RNA 2'-phosphodiester yields 2'-OH RNA and ADP-ribose-1,2-cyclic phosphate. Here, we present structures of archaeal Tpt1 enzymes, captured as product complexes with ADP-ribose-1-PO(4), ADP-ribose-2-PO(4), and 2'-OH RNA, and as substrate complexes with 2',5'-ADP and NAD(+), that illuminate 2'-PO(4) junction recognition and catalysis. We show that archaeal Tpt1 enzymes can use the 2'-PO(4)-containing metabolites NADP(+) and NADPH as substrates for 2'-PO(4) transfer to NAD(+). A role in 2'-phospho-NADP(H) dynamics provides a rationale for the prevalence of Tpt1 in taxa that lack a capacity for internal RNA 2'-phosphorylation.
Structural basis for Tpt1-catalyzed 2'-PO(4) transfer from RNA and NADP(H) to NAD().,Jacewicz A, Dantuluri S, Shuman S Proc Natl Acad Sci U S A. 2023 Oct 31;120(44):e2312999120. doi: , 10.1073/pnas.2312999120. Epub 2023 Oct 26. PMID:37883434[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jacewicz A, Dantuluri S, Shuman S. Structural basis for Tpt1-catalyzed 2'-PO(4) transfer from RNA and NADP(H) to NAD(). Proc Natl Acad Sci U S A. 2023 Oct 31;120(44):e2312999120. PMID:37883434 doi:10.1073/pnas.2312999120
