Crystal structure of human ADP-ribose transferase ARTD15/PARP16 reveals a novel putative regulatory domain.
ADP-ribosylation is involved in the regulation of DNA repair, transcription, and other processes. The 18 human ADP-ribose transferases with diphtheria toxin homology include ARTD1/PARP1, a cancer drug target. Knowledge of other family members may guide therapeutics development and help evaluate potential drug side effects. Here, we present the crystal structure of human ARTD15/PARP16, a previously uncharacterized enzyme. ARTD15 features an α-helical domain that packs against its transferase domain without making direct contact with the NAD(+)-binding crevice or the donor loop. Thus, this novel domain does not resemble the regulatory domain of ARTD1. ARTD15 displays auto-mono(ADP-ribosylation) activity and is affected by canonical poly(ADP-ribose) polymerase inhibitors. These results add to a framework that will facilitate research on a medically important family of enzymes.
Structural Genomics Consortium, Karolinska Institutet, 17177 Stockholm, Sweden.
Tobias
T
Karlberg
Ann-Gerd
AG
Thorsell
Åsa
Å
Kallas
Herwig
H
Schüler
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D011065:Poly(ADP-ribose) Polymerases