 |
PDBsum entry 5fe0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein
|
PDB id
|
|
|
|
5fe0
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Signaling protein
|
|
|
Title:
|
|
Crystal structure of human pcaf bromodomain in complex with acetyllysine
|
|
Structure:
|
|
Histone acetyltransferase kat2b. Chain: a, b. Fragment: pcaf bromodomain, unp residues 715-831. Synonym: histone acetyltransferase pcaf,histone acetylase pcaf,lysine acetyltransferase 2b,p300/cbp-associated factor,p/caf. Engineered: yes
|
|
Source:
|
|
Homo sapiens. Human. Organism_taxid: 9606. Gene: kat2b, pcaf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: r3-prare2
|
|
Resolution:
|
|
|
2.30Å
|
R-factor:
|
0.211
|
R-free:
|
0.246
|
|
|
Authors:
|
|
A.Chaikuad,F.Von Delft,C.Bountra,C.H.Arrowsmith,A.M.Edwards,S.Knapp, Structural Genomics Consortium (Sgc)
|
|
Key ref:
|
|
A.Chaikuad
et al.
(2016).
Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.
J Med Chem,
59,
1648-1653.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
16-Dec-15
|
Release date:
|
13-Jan-16
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q92831
(KAT2B_HUMAN) -
Histone acetyltransferase KAT2B from Homo sapiens
|
|
|
|
Seq:
Struc:
|
|
|
|
832 a.a.
108 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
|
|
|
|
|
|
|
|
|
|
|
Enzyme class 1:
|
|
E.C.2.3.1.48
- histone acetyltransferase.
|
|
|
|
|
|
|
Reaction:
|
|
L-lysyl-[protein] + acetyl-CoA = N6-acetyl-L-lysyl-[protein] + CoA + H+
|
|
|
|
|
|
L-lysyl-[protein]
|
+
|
acetyl-CoA
|
=
|
N(6)-acetyl-L-lysyl-[protein]
|
+
|
CoA
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
Enzyme class 2:
|
|
E.C.2.3.1.57
- diamine N-acetyltransferase.
|
|
|
|
|
|
|
Reaction:
|
|
an alkane-alpha,omega-diamine + acetyl-CoA = an N-acetylalkane- alpha,omega-diamine + CoA + H+
|
|
|
|
|
|
alkane-alpha,omega-diamine
|
+
|
acetyl-CoA
|
=
|
N-acetylalkane- alpha,omega-diamine
|
+
|
CoA
|
+
|
H(+)
|
|
|
|
|
|
|
|
|
|
|
|
|
Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
J Med Chem
59:1648-1653
(2016)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain.
|
|
A.Chaikuad,
S.Lang,
P.E.Brennan,
C.Temperini,
O.Fedorov,
J.Hollander,
R.Nachane,
C.Abell,
S.Müller,
G.Siegal,
S.Knapp.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The P300/CBP-associated factor plays a central role in retroviral infection and
cancer development, and the C-terminal bromodomain provides an opportunity for
selective targeting. Here, we report several new classes of acetyl-lysine
mimetic ligands ranging from mM to low micromolar affinity that were identified
using fragment screening approaches. The binding modes of the most attractive
fragments were determined using high resolution crystal structures providing
chemical starting points and structural models for the development of potent and
selective PCAF inhibitors.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
