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PDBsum entry 5mw2
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Transcription
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PDB id
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5mw2
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PDB id:
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| Name: |
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Transcription
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Title:
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Crystal structure of bcl-6 btb-domain with bi-3802
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Structure:
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B-cell lymphoma 6 protein. Chain: a. Synonym: bcl-6,b-cell lymphoma 5 protein,bcl-5,protein laz-3,zinc finger and btb domain-containing protein 27,zinc finger protein 51
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Source:
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Fragment: corresponding to PDB id 1r28. Obtained from emerald bi... Homo sapiens. Human. Organism_taxid: 9606. Other_details: bind crystal_id 1008303
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Resolution:
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2.35Å
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R-factor:
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0.249
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R-free:
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0.283
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Authors:
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G.Bader,G.Flotzinger,A.Weiss-Puxbaum,A.Zoephel
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Key ref:
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N.Kerres
et al.
(2017).
Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6.
Cell Rep,
20,
2860-2875.
PubMed id:
DOI:
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Date:
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18-Jan-17
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Release date:
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04-Oct-17
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PROCHECK
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Headers
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References
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P41182
(BCL6_HUMAN) -
B-cell lymphoma 6 protein from Homo sapiens
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Seq:
Struc:
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706 a.a.
122 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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DOI no:
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Cell Rep
20:2860-2875
(2017)
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PubMed id:
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Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6.
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N.Kerres,
S.Steurer,
S.Schlager,
G.Bader,
H.Berger,
M.Caligiuri,
C.Dank,
J.R.Engen,
P.Ettmayer,
B.Fischerauer,
G.Flotzinger,
D.Gerlach,
T.Gerstberger,
T.Gmaschitz,
P.Greb,
B.Han,
E.Heyes,
R.E.Iacob,
D.Kessler,
H.Kölle,
L.Lamarre,
D.R.Lancia,
S.Lucas,
M.Mayer,
K.Mayr,
N.Mischerikow,
K.Mück,
C.Peinsipp,
O.Petermann,
U.Reiser,
D.Rudolph,
K.Rumpel,
C.Salomon,
D.Scharn,
R.Schnitzer,
A.Schrenk,
N.Schweifer,
D.Thompson,
E.Traxler,
R.Varecka,
T.Voss,
A.Weiss-Puxbaum,
S.Winkler,
X.Zheng,
A.Zoephel,
N.Kraut,
D.McConnell,
M.Pearson,
M.Koegl.
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ABSTRACT
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The transcription factor BCL6 is a known driver of oncogenesis in lymphoid
malignancies, including diffuse large B cell lymphoma (DLBCL). Disruption of its
interaction with transcriptional repressors interferes with the oncogenic
effects of BCL6. We used a structure-based drug design to develop highly potent
compounds that block this interaction. A subset of these inhibitors also causes
rapid ubiquitylation and degradation of BCL6 in cells. These compounds display
significantly stronger induction of expression of BCL6-repressed genes and
anti-proliferative effects than compounds that merely inhibit co-repressor
interactions. This work establishes the BTB domain as a highly druggable
structure, paving the way for the use of other members of this protein family as
drug targets. The magnitude of effects elicited by this class of BCL6-degrading
compounds exceeds that of our equipotent non-degrading inhibitors, suggesting
opportunities for the development of BCL6-based lymphoma therapeutics.
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