6E3A

tRNA 2'-phosphotransferase

Summary for 6E3A

• Entry DOI: 10.2210/pdb6e3a/pdb
• Descriptor: Probable RNA 2'-phosphotransferase, COENZYME A, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-phosphonooxy-oxolan-2-yl]methyl hydrogen phosphate, ... (4 entities in total)
• Functional Keywords: kpta, tpt1, trpt1, transferase
• Biological source: Clostridium thermocellum (strain ATCC 27405 / DSM 1237 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) (Ruminiclostridium thermocellum)
• Total number of polymer chains: 1
• Total formula weight: 22556.29

Authors

Shuman, S.,Goldgur, Y.,Banerjee, A. (deposition date: 2018-07-13, release date: 2019-03-20, Last modification date: 2024-10-23)

Primary citation

Banerjee, A.,Munir, A.,Abdullahu, L.,Damha, M.J.,Goldgur, Y.,Shuman, S.
Structure of tRNA splicing enzyme Tpt1 illuminates the mechanism of RNA 2'-PO4recognition and ADP-ribosylation.
Nat Commun, 10:218-218, 2019

PubMed Abstract: Tpt1 is an essential agent of fungal tRNA splicing that removes the 2'-PO at the splice junction generated by fungal tRNA ligase. Tpt1 catalyzes a unique two-step reaction whereby the 2'-PO attacks NAD to form an RNA-2'-phospho-ADP-ribosyl intermediate that undergoes transesterification to yield 2'-OH RNA and ADP-ribose-1″,2″-cyclic phosphate products. Because Tpt1 is inessential in exemplary bacterial and mammalian taxa, Tpt1 is seen as an attractive antifungal target. Here we report a 1.4 Å crystal structure of Tpt1 in a product-mimetic complex with ADP-ribose-1″-phosphate in the NAD site and pAp in the RNA site. The structure reveals how Tpt1 recognizes a 2'-PO RNA splice junction and the mechanism of RNA phospho-ADP-ribosylation. This study also provides evidence that a bacterium has an endogenous phosphorylated substrate with which Tpt1 reacts.

PubMed: 30644400
DOI: 10.1038/s41467-018-08211-9

Experimental method

X-RAY DIFFRACTION (1.4 Å)