Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T86399 Target Info
Target Name Bromodomain-containing protein 2 (BRD2)
Synonyms Really interesting new gene 3 protein; RING3; O27.1.1; KIAA9001
Target Type Clinical trial Target
Gene Name BRD2
Biochemical Class Bromodomain
UniProt ID
BRD2_HUMAN
Ligand General Information  Top
Ligand Name ME bromodomain inhibitor Ligand Info
Canonical SMILES CC1=NN=C2N1C3=C(C=C(C=C3)OC)C(=NC2C(C)C(=O)OC)C4=CC=C(C=C4)Cl
InChI 1S/C22H21ClN4O3/c1-12(22(28)30-4)19-21-26-25-13(2)27(21)18-10-9-16(29-3)11-17(18)20(24-19)14-5-7-15(23)8-6-14/h5-12,19H,1-4H3/t12-,19+/m1/s1
InChIKey FENXDXHDXYVGRJ-BLVKFPJESA-N
PubChem Compound ID 86277842
Drug Binding Sites of Target  Top
PDB ID: 5O39      Human Brd2(BD2) mutant in complex with ME
Method X-ray diffraction Resolution 1.74 Å Mutation Yes [1]
PDB Sequence
GKLSEQLKHC
353
NGILKELLSK
363
KHAAYAWPFY
373
KPVDASALGV
383
HDYHDIIKHP
393

MDLSTVKRKM
403
ENRDYRDAQE
413
FAADVRLMFS
423
NCYKYNPPDH
433
DVVAMARKLQ
443

DVFEFRYAKM
453
PD
Residue
Distance (Å)
TRP370
3.092
PRO371
2.943
PHE372
2.999
LYS374
4.651
PRO375
4.942
VAL376
3.298
LEU381
3.155
VAL383
2.668
Residue
Distance (Å)
TYR386
3.444
CYS425
3.757
TYR428
2.804
ASN429
2.504
ASP434
3.745
VAL435
3.251
MET438
3.050
PDB ID: 4QEV      Crystal structure of BRD2(BD2) mutant with ligand ME bound (METHYL (2R)- 2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1, 4]BENZODIAZEPIN-4-YL]PROPANOATE)
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [2]
PDB Sequence
LSEQLKHCNG
355
ILKELLSKKH
365
AAYAWPFYKP
375
VDASALGAHD
385
YHDIIKHPMD
395

LSTVKRKMEN
405
RDYRDAQEFA
415
ADVRLMFSNC
425
YKYNPPDHDV
435
VAMARKLQDV
445

FEFRYAKMPD
455
Residue
Distance (Å)
TRP370
3.396
PRO371
3.389
PHE372
3.559
VAL376
4.065
LEU381
4.057
ALA383
3.792
TYR386
3.819
Residue
Distance (Å)
CYS425
4.173
TYR428
3.261
ASN429
3.089
ASP434
3.950
VAL435
3.579
MET438
4.187
References  Top
REF 1 Optimization of a "bump-and-hole" approach to allele-selective BET bromodomain inhibition. Chem Sci. 2018 Jan 24;9(9):2452-2468.
REF 2 Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science. 2014 Oct 31;346(6209):638-41.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.