 |
PDBsum entry 3c49
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Transferase
|
|
|
Title:
|
|
Human poly(adp-ribose) polymerase 3, catalytic fragment in complex with an inhibitor ku0058948
|
|
Structure:
|
|
Poly(adp-ribose) polymerase 3. Chain: a. Fragment: catalytic fragment: residues 178-532. Synonym: parp-3, NAD(+) adp-ribosyltransferase 3, poly[adp-ribose] synthetase 3, padprt-3, hparp-3, irt1. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: parp3, adprt3, adprtl3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
|
|
Resolution:
|
|
|
2.80Å
|
R-factor:
|
0.191
|
R-free:
|
0.257
|
|
|
Authors:
|
|
L.Lehtio,T.Karlberg,C.H.Arrowsmith,H.Berglund,C.Bountra,R.Busam, R.Collins,L.G.Dahlgren,A.M.Edwards,S.Flodin,A.Flores,S.Graslund, M.Hammarstrom,T.Helleday,M.D.Herman,A.Johansson,I.Johansson, A.Kallas,T.Kotenyova,M.Moche,M.E.Nilsson,P.Nordlund,T.Nyman, C.Persson,J.Sagemark,L.Svensson,A.G.Thorsell,L.Tresaugues,S.Van Den Berg,M.Welin,J.Weigelt,Structural Genomics Consortium (Sgc)
|
|
Key ref:
|
|
L.Lehtiö
et al.
(2009).
Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
J Med Chem,
52,
3108-3111.
PubMed id:
|
|
|
Date:
|
|
|
29-Jan-08
|
Release date:
|
12-Feb-08
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q9Y6F1
(PARP3_HUMAN) -
Protein mono-ADP-ribosyltransferase PARP3 from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
533 a.a.
357 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
J Med Chem
52:3108-3111
(2009)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
|
|
L.Lehtiö,
A.S.Jemth,
R.Collins,
O.Loseva,
A.Johansson,
N.Markova,
M.Hammarström,
A.Flores,
L.Holmberg-Schiavone,
J.Weigelt,
T.Helleday,
H.Schüler,
T.Karlberg.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress-
and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in
cancer drug therapy. We present a structural and functional analysis of the PARP
domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948
is the strongest inhibitor of PARP-3 activity. The presented crystal structures
highlight key features for potent inhibitor binding and suggest routes for
creating isoenzyme-specific PARP inhibitors.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.Mangerich,
and
A.Bürkle
(2011).
How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation.
|
| |
Int J Cancer,
128,
251-265.
|
|
|
|
|
|
|
C.Boehler,
L.R.Gauthier,
O.Mortusewicz,
D.S.Biard,
J.M.Saliou,
A.Bresson,
S.Sanglier-Cianferani,
S.Smith,
V.Schreiber,
F.Boussin,
and
F.Dantzer
(2011).
Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression.
|
| |
Proc Natl Acad Sci U S A,
108,
2783-2788.
|
|
|
|
|
|
|
J.X.He,
C.H.Yang,
and
Z.H.Miao
(2010).
Poly(ADP-ribose) polymerase inhibitors as promising cancer therapeutics.
|
| |
Acta Pharmacol Sin,
31,
1172-1180.
|
|
|
|
|
|
|
M.O.Hottiger,
P.O.Hassa,
B.Lüscher,
H.Schüler,
and
F.Koch-Nolte
(2010).
Toward a unified nomenclature for mammalian ADP-ribosyltransferases.
|
| |
Trends Biochem Sci,
35,
208-219.
|
|
|
|
|
|
|
M.Rouleau,
A.Patel,
M.J.Hendzel,
S.H.Kaufmann,
and
G.G.Poirier
(2010).
PARP inhibition: PARP1 and beyond.
|
| |
Nat Rev Cancer,
10,
293-301.
|
|
|
|
|
|
|
O.Loseva,
A.S.Jemth,
H.E.Bryant,
H.Schüler,
L.Lehtiö,
T.Karlberg,
and
T.Helleday
(2010).
PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA.
|
| |
J Biol Chem,
285,
8054-8060.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
|
|
Links
