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

Karlberg, Tobias LU ; Thorsell, Ann-Gerd ; Kallas, Åsa and Schüler, Herwig LU orcid (2012) In The Journal of biological chemistry 287(29). p.81-24077
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 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... (More)

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.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Amino Acid Sequence, Crystallography, X-Ray/methods, Humans, Molecular Sequence Data, Poly(ADP-ribose) Polymerases/chemistry, Protein Structure, Tertiary/genetics, Sequence Homology, Amino Acid
in
The Journal of biological chemistry
volume
287
issue
29
pages
5 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:22661712
  • scopus:84863804147
ISSN
1083-351X
DOI
10.1074/jbc.M112.379289
language
English
LU publication?
no
id
9b8e62e3-a5b1-4f0c-ad59-46977e2d4ffd
date added to LUP
2024-11-21 17:57:57
date last changed
2025-01-03 07:44:21
@article{9b8e62e3-a5b1-4f0c-ad59-46977e2d4ffd,
  abstract     = {{<p>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.</p>}},
  author       = {{Karlberg, Tobias and Thorsell, Ann-Gerd and Kallas, Åsa and Schüler, Herwig}},
  issn         = {{1083-351X}},
  keywords     = {{Amino Acid Sequence; Crystallography, X-Ray/methods; Humans; Molecular Sequence Data; Poly(ADP-ribose) Polymerases/chemistry; Protein Structure, Tertiary/genetics; Sequence Homology, Amino Acid}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{29}},
  pages        = {{81--24077}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{The Journal of biological chemistry}},
  title        = {{Crystal structure of human ADP-ribose transferase ARTD15/PARP16 reveals a novel putative regulatory domain}},
  url          = {{http://dx.doi.org/10.1074/jbc.M112.379289}},
  doi          = {{10.1074/jbc.M112.379289}},
  volume       = {{287}},
  year         = {{2012}},
}