Crystal Structure of Human ADP-ribose Transferase ARTD15/PARP16 Reveals a Novel Putative Regulatory Domain
| Autor: | Åsa Kallas, Herwig Schüler, Ann-Gerd Thorsell, Tobias Karlberg |
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| Rok vydání: | 2012 |
| Předmět: |
Sequence Homology
Amino Acid biology Effector Poly ADP ribose polymerase Molecular Sequence Data Protein domain Cell Biology Crystallography X-Ray Biochemistry Protein Structure Tertiary Protein structure ADP-ribosylation Protein Structure and Folding biology.protein Humans Transferase Amino Acid Sequence NAD+ kinase Poly(ADP-ribose) Polymerases Molecular Biology Polymerase |
| Zdroj: | Journal of Biological Chemistry. 287:24077-24081 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.379289 |
| Popis: | 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. Background: ADP-ribose transferases ARTD1–3/PARP1–3 have an α-helical domain that closes over the NAD+-binding site. Results: Human ARTD15/PARP16 is a mono(ADP-ribose) transferase with a novel α-helical domain that interacts with a catalytic domain loop. Conclusion: The ARTD15 transferase domain is likely regulated by effector binding to the adjacent helical domain. Significance: This provides a basis for understanding the enzymatic mechanism of this previously uncharacterized enzyme. |
| Databáze: | OpenAIRE |
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