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 T30420 Target Info
Target Name SET domain containing 8 (KMT5A)
Synonyms SETD8; SET8; SET07; SET domain-containing protein 8; PRSET7; PR/SET07; PR/SET domain-containing protein 07; PR-Set7; N-lysine methyltransferase KMT5A; Lysine-specific methylase 5A; Lysine N-methyltransferase 5A; Histone-lysine N-methyltransferase KMT5A; H4-K20-HMTase KMT5A
Target Type Preclinical Target
Gene Name KMT5A
Biochemical Class Methyltransferase
UniProt ID
KMT5A_HUMAN
Ligand General Information  Top
Ligand Name Ademetionine Ligand Info
Canonical SMILES C[S+](CCC(C(=O)[O-])N)CC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)O
InChI 1S/C15H22N6O5S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25)/t7-,8+,10+,11+,14+,27?/m0/s1
InChIKey MEFKEPWMEQBLKI-AIRLBKTGSA-N
PubChem Compound ID 34755
Drug Binding Sites of Target  Top
PDB ID: 7XPX      Cryo-EM structure of the histone methyltransferase SET8 bound to H4K20Ecx-nucleosome
Method Electron microscopy Resolution 3.20 Å Mutation Yes [1]
PDB Sequence
PVRRSSRKSK
195
AELQSEERKR
205
IDELIESGKE
215
EGMKIDLIDG
225
KGRGVIATKQ
235

FSRGDFVVEY
245
HGDLIEITDA
255
KKREALYAQD
265
PSTGCYMYYF
275
QYLSKTYCVD
285

ATRETNRLGR
295
LINHSKCGNC
305
QTKLHDIDGV
315
PHLILIASRD
325
IAAGEELLYD
335

YGDRSKASIE
345
AHPWLKH
Residue
Distance (Å)
GLY225
3.064
LYS226
2.949
GLY227
3.819
ARG228
2.646
TYR245
4.731
CYS270
3.872
TYR271
3.385
ARG295
3.364
Residue
Distance (Å)
LEU296
3.838
ILE297
3.709
ASN298
3.899
HIS299
3.087
TYR334
4.766
TYR336
3.179
HIS347
3.221
TRP349
3.503
PDB ID: 4IJ8      Crystal structure of the complex of SETD8 with SAM
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [2]
PDB Sequence
RKSKAELQSE
242
ERKRIDELIE
252
SGKEEGMKID
262
LIDGKGRGVI
272
ATKQFSRGDF
282

VVEYHGDLIE
292
ITDAKKREAL
302
YAQDPSTGCY
312
MYYFQYLSKT
322
YCVDATRETN
332

RLGRLINHSK
342
SGNCQTKLHD
352
IDGVPHLILI
362
ASRDIAAGEE
372
LLYDYGDRSK
382

ASIEAHPWLK
392
H
Residue
Distance (Å)
GLY266
3.156
LYS267
2.808
GLY268
3.993
ARG269
2.735
CYS311
3.086
TYR312
2.711
ARG336
3.123
Residue
Distance (Å)
LEU337
3.445
ILE338
3.693
ASN339
2.951
HIS340
2.858
TYR377
3.409
HIS388
4.158
TRP390
3.416
PDB ID: 5TEG      Crystal structure of hSETD8 in complex with histone H4K20 norleucine mutant peptide and S-Adenosylmethionine
Method X-ray diffraction Resolution 1.30 Å Mutation Yes [3]
PDB Sequence
KSKAELQSEE
202
RKRIDELIES
212
GKEEGMKIDL
222
IDGKGRGVIA
232
TKQFSRGDFV
242

VEYHGDLIEI
252
TDAKKREALY
262
AQDPSTGCYM
272
YYFQYLSKTY
282
CVDATRETNR
292

LGRLINHSKS
302
GNCQTKLHDI
312
DGVPHLILIA
322
SRDIAAGEEL
332
LYDYGDRSKA
342

SIEAHPWLKH
352
Residue
Distance (Å)
GLY225
3.416
LYS226
2.727
GLY227
3.916
ARG228
2.772
TYR245
4.623
CYS270
3.654
TYR271
2.582
ARG295
3.234
Residue
Distance (Å)
LEU296
3.413
ILE297
3.627
ASN298
2.865
HIS299
2.928
TYR336
3.347
HIS347
4.766
TRP349
3.334
References  Top
REF 1 Structural basis of nucleosomal H4K20 methylation by methyltransferase SET8. FASEB J. 2022 Jun;36(6):e22338.
REF 2 Crystal structure of the complex of SETD8 with SAM
REF 3 Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8. ACS Med Chem Lett. 2016 Oct 11;7(12):1102-1106.

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