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Crystal structure of human ADP-ribose transferase ARTD15/PARP16 reveals a novel putative regulatory domain.

ABSTRACT: 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 ?-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.

SUBMITTER: Karlberg T

PROVIDER: S-EPMC3397834 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Crystal structure of human ADP-ribose transferase ARTD15/PARP16 reveals a novel putative regulatory domain.

Karlberg Tobias T Thorsell Ann-Gerd AG Kallas Åsa Å Schüler Herwig H

The Journal of biological chemistry 20120601 29

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 doma ...[more]

PMID: 22661712

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