Structural Basis for Lack of ADP-ribosyltransferase Activity in Poly(ADP-ribose) Polymerase-13/Zinc Finger Antiviral Protein

Abstract

Background: PARP13 contains a divergent PARP homology ADP-ribosyltransferase domain of unknown function. Results: The consensus NAD ϩ pocket of PARP13 is occluded by interacting protein side chains.

Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors

“…This flexible moiety has been observed in yet a different conformation in PARP3, 42 and binding of PJ34 to two distinct sites has been observed in tankyrase-2. 43 We have solved a complex of PARP15−PJ34 earlier 44 and a structure of Pseudomonas aeruginosa ExoA−PJ34 has also been published. 45 Comparison of the crystal structure of the PARP1–PJ34 complex with those structures shows that the terminal dimethyl glycinamide moiety confers flexible van der Waals interaction propensity, enabling the compound to interact with nonpolar surfaces on either side of the NAD + binding crevice.…”

TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control

“…4D-F). TASOR shares a further similarity with ZAP/PARP13, in that the equivalent of its active site loop or D-loop (TASOR residues 200-210) adopts a closed conformation relative to PARP1, in which it is open (Karlberg et al, 2015;Langelier et al, 2018) (Fig. 4E,F).…”

“…The other residues involved in NAD + binding are conserved in active PARPs, regardless of whether activity is mono-or poly-ADP ribosylation. By contrast, the human zinc finger antiviral protein (HsZAP, or PARP13) and Arabidopsis RCD1 lack two or more of the NAD + -binding residues and are catalytically inactive (Karlberg et al, 2015;Wirthmueller et al, 2018). In TASOR the key residues required for catalysis are even more degenerated than in ZAP or RCD1: all but one of them are replaced by hydrophobic amino acids ( Fig.…”

Detection of piRNAs in whitespotted bamboo shark liver

“…pi-6084, which had the most GO annotations, may have more than three functions: 1) acting on the immune response since its target gene, collection of sub-family member 10 (COLEC10) (Dong et al, 2004;Bayarri-Olmos et al, 2015), can bind carbohydrates; 2) playing important roles in development, angiogenesis and coagulation because one of its target genes belong to a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS18) (Wei et al, 2014;Xu et al, 2015); and 3) taking part in the synthesis of dystrophin with the role of actin binding because its third target gene is DMD. pi-33352 had three target genes and thus three types of functions: 1) roles in viral immunity and stress responses because the target gene named PARP7 is able to bind zinc ions and exhibits NAD + ADP-ribosyl transferase activity as a poly[ADP-ribose]polymerase 7/11/12/13 (Ame et al, 2004;Welsby et al, 2014;Karlberg et al, 2015); 2) participating in the proline catabolic process because its second target gene is proline dehydrogenase 2 (PRODH2), which expresses hydroxyproline oxidase; and 3) taking part in the regulation of developing synapses since its third target gene is SH3 and multiple ankyrin repeated domain protein gene (SHANK3) (Benthani et al, 2015;Cochoy et al, 2015). However, pi-3061, which has three target genes, may have only one target gene named RAPGEF4.…”