|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Cell cycle
|
|
|
Title:
|
|
Structure of the human mdmx protein bound to the p53 tumor suppressor transactivation domain
|
|
Structure:
|
|
Mdm4 protein. Chain: m, a. Fragment: unp residues 15-129. Synonym: p53-binding protein mdm4, mdm2-like p53-binding protein, protein mdmx, double minute 4 protein. Engineered: yes. Mutation: yes. Cellular tumor antigen p53. Chain: p, b.
|
|
Source:
|
|
Danio rerio. Zebrafish. Organism_taxid: 7955. Gene: mdm4, mdmx. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide
|
|
Resolution:
|
|
|
1.80Å
|
R-factor:
|
0.207
|
R-free:
|
0.243
|
|
|
Authors:
|
|
G.M.Popowicz,A.Czarna,T.A.Holak
|
|
Key ref:
|
|
G.M.Popowicz
et al.
(2008).
Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.
Cell Cycle,
7,
2441-2443.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
29-May-08
|
Release date:
|
02-Sep-08
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q7ZUW7
(MDM4_DANRE) -
Protein Mdm4 from Danio rerio
|
|
|
|
Seq:
Struc:
|
|
|
|
496 a.a.
85 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Cell Cycle
7:2441-2443
(2008)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.
|
|
G.M.Popowicz,
A.Czarna,
T.A.Holak.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The Mdmx oncoprotein has only recently emerged as a critical-independent to
Mdm2-regulator of p53 activation. We have determined the crystal structure of
the N-terminal domain of human Mdmx bound to a 15-residue transactivation domain
peptide of human p53. The structure shows why antagonists of the Mdm2 binding to
p53 are ineffective in the Mdmx-p53 interaction.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
C.F.Cheok,
C.S.Verma,
J.Baselga,
and
D.P.Lane
(2011).
Translating p53 into the clinic.
|
| |
Nat Rev Clin Oncol,
8,
25-37.
|
|
|
|
|
|
|
A.C.Joerger,
and
A.R.Fersht
(2010).
The tumor suppressor p53: from structures to drug discovery.
|
| |
Cold Spring Harb Perspect Biol,
2,
a000919.
|
|
|
|
|
|
|
B.Xue,
R.L.Dunbrack,
R.W.Williams,
A.K.Dunker,
and
V.N.Uversky
(2010).
PONDR-FIT: a meta-predictor of intrinsically disordered amino acids.
|
| |
Biochim Biophys Acta,
1804,
996.
|
|
|
|
|
|
|
C.Li,
M.Pazgier,
C.Li,
W.Yuan,
M.Liu,
G.Wei,
W.Y.Lu,
and
W.Lu
(2010).
Systematic mutational analysis of peptide inhibition of the p53-MDM2/MDMX interactions.
|
| |
J Mol Biol,
398,
200-213.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
F.Bernal,
M.Wade,
M.Godes,
T.N.Davis,
D.G.Whitehead,
A.L.Kung,
G.M.Wahl,
and
L.D.Walensky
(2010).
A stapled p53 helix overcomes HDMX-mediated suppression of p53.
|
| |
Cancer Cell,
18,
411-422.
|
|
|
|
|
|
|
J.Phan,
Z.Li,
A.Kasprzak,
B.Li,
S.Sebti,
W.Guida,
E.Schönbrunn,
and
J.Chen
(2010).
Structure-based design of high affinity peptides inhibiting the interaction of p53 with MDM2 and MDMX.
|
| |
J Biol Chem,
285,
2174-2183.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
E.A.Harker,
D.S.Daniels,
D.A.Guarracino,
and
A.Schepartz
(2009).
Beta-peptides with improved affinity for hDM2 and hDMX.
|
| |
Bioorg Med Chem,
17,
2038-2046.
|
|
|
|
|
|
|
F.Mancini,
G.D.Conza,
and
F.Moretti
(2009).
MDM4 (MDMX) and its Transcript Variants.
|
| |
Curr Genomics,
10,
42-50.
|
|
|
|
|
|
|
H.Feng,
L.M.Jenkins,
S.R.Durell,
R.Hayashi,
S.J.Mazur,
S.Cherry,
J.E.Tropea,
M.Miller,
A.Wlodawer,
E.Appella,
and
Y.Bai
(2009).
Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation.
|
| |
Structure,
17,
202-210.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.A.Robinson
(2009).
Design of protein-protein interaction inhibitors based on protein epitope mimetics.
|
| |
Chembiochem,
10,
971-973.
|
|
|
|
|
|
|
J.Kallen,
A.Goepfert,
A.Blechschmidt,
A.Izaac,
M.Geiser,
G.Tavares,
P.Ramage,
P.Furet,
K.Masuya,
and
J.Lisztwan
(2009).
Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues Reveal Surprising Conformational Changes.
|
| |
J Biol Chem,
284,
8812-8821.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Pazgier,
M.Liu,
G.Zou,
W.Yuan,
C.Li,
C.Li,
J.Li,
J.Monbo,
D.Zella,
S.G.Tarasov,
and
W.Lu
(2009).
Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX.
|
| |
Proc Natl Acad Sci U S A,
106,
4665-4670.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Wade,
and
G.M.Wahl
(2009).
Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry?
|
| |
Mol Cancer Res,
7,
1.
|
|
|
|
|
|
|
R.Hayashi,
D.Wang,
T.Hara,
J.A.Iera,
S.R.Durell,
and
D.H.Appella
(2009).
N-acylpolyamine inhibitors of HDM2 and HDMX binding to p53.
|
| |
Bioorg Med Chem,
17,
7884-7893.
|
|
|
|
|
|
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.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
 |
|
Links
