Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T83904 Target Info
Target Name NAD-dependent deacetylase sirtuin-2 (SIRT2)
Synonyms SIR2like protein 2; SIR2L2; SIR2L; SIR2-like protein 2; Regulatory protein SIR2 homolog 2; NADdependent protein deacetylase sirtuin2; NAD-dependent protein deacetylase sirtuin-2
Target Type Patented-recorded Target
Gene Name SIRT2
Biochemical Class Carbon-nitrogen hydrolase
UniProt ID
SIR2_HUMAN
Ligand General Information  Top
Ligand Name Nicotinamide-Adenine-Dinucleotide Ligand Info
Canonical SMILES C1=CC(=C[N+](=C1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)N4C=NC5=C(N=CN=C54)N)O)O)O)O)C(=O)N
InChI 1S/C21H27N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1-4,7-8,10-11,13-16,20-21,29-32H,5-6H2,(H5-,22,23,24,25,33,34,35,36,37)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
InChIKey BAWFJGJZGIEFAR-NNYOXOHSSA-N
PubChem Compound ID 5892
Drug Binding Sites of Target  Top
PDB ID: 5DY4      Crystal structure of human Sirt2 in complex with a brominated 2nd generation SirReal inhibitor and NAD+
Method X-ray diffraction Resolution 1.77 Å Mutation No [1]
PDB Sequence
GHMERLLDEL
62
TLEGVARYMQ
72
SERCRRVICL
82
VGAGISTSAG
92
IPDFRSGLYD
105

NLEKYHLPYP
115
EAIFEISYFK
125
KHPEPFFALA
135
KELYPGQFKP
145
TICHYFMRLL
155

KDKGLLLRCY
165
TQNIDTLERI
175
AGLEQEDLVE
185
AHGTFYTSHC
195
VSASCRHEYP
205

LSWMKEKIFS
215
EVTPKCEDCQ
225
SLVKPDIVFF
235
GESLPARFFS
245
CMQSDFLKVD
255

LLLVMGTSLQ
265
VQPFASLISK
275
APLSTPRLLI
285
NKEKAGQSDP
295
FLGMIMGLGG
305

GMDFDSKKAY
315
RDVAWLGECD
325
QGCLALAELL
335
GWKKELEDLV
345
RREHASIDAQ
355

S
Residue
Distance (Å)
VAL83
4.985
GLY84
3.068
ALA85
3.025
GLY86
3.279
SER88
3.756
THR89
2.809
SER90
4.660
ILE93
3.637
PRO94
3.298
ASP95
3.183
PHE96
3.872
ARG97
2.882
GLN167
2.489
ASN168
3.306
ILE169
2.887
Residue
Distance (Å)
ASP170
2.752
HIS187
2.698
GLY261
3.362
THR262
2.653
SER263
2.616
LEU264
4.374
VAL266
4.038
ILE285
4.828
ASN286
3.215
LYS287
3.124
GLU288
2.594
GLY322
3.341
GLU323
3.434
CYS324
2.847
PDB ID: 4RMG      Human Sirt2 in complex with SirReal2 and NAD+
Method X-ray diffraction Resolution 1.88 Å Mutation No [2]
PDB Sequence
HMERLLDELT
63
LEGVARYMQS
73
ERCRRVICLV
83
GAGISTSAGI
93
PDFRSPLYDN
106

LEKYHLPYPE
116
AIFEISYFKK
126
HPEPFFALAK
136
ELYPGQFKPT
146
ICHYFMRLLK
156

DKGLLLRCYT
166
QNIDTLERIA
176
GLEQEDLVEA
186
HGTFYTSHCV
196
SASCRHEYPL
206

SWMKEKIFSE
216
VTPKCEDCQS
226
LVKPDIVFFG
236
ESLPARFFSC
246
MQSDFLKVDL
256

LLVMGTSLQV
266
QPFASLISKA
276
PLSTPRLLIN
286
KEKAGQSDGM
299
IMGLGGGMDF
309

DSKKAYRDVA
319
WLGECDQGCL
329
ALAELLGWKK
339
ELEDLVRREH
349
ASIDAQS
Residue
Distance (Å)
VAL83
4.691
GLY84
2.750
ALA85
2.853
GLY86
2.963
SER88
3.716
THR89
2.926
SER90
4.624
ILE93
3.549
PRO94
3.298
ASP95
3.301
PHE96
3.677
GLN167
2.452
ASN168
3.252
ILE169
2.670
Residue
Distance (Å)
ASP170
2.573
HIS187
2.496
GLY261
3.223
THR262
2.761
SER263
2.718
LEU264
4.546
PHE269
4.894
ILE285
4.815
ASN286
3.102
LYS287
3.030
GLU288
2.544
GLY322
3.366
GLU323
3.195
CYS324
2.760
PDB ID: 6L66      Sirtuin 2 protein with H3K18 myristoylated peptide and intact NAD molecule
Method X-ray diffraction Resolution 2.17 Å Mutation No [3]
PDB Sequence
GSQKERLLDE
61
LTLEGVARYM
71
QSQRCRRVIC
81
LVGAGISTSA
91
GIPDFRSPST
101

GLYDNLEKYH
111
LPYPEAIFEI
121
SYFKKHPEPF
131
FALAKELYPG
141
QFKPTICHYF
151

MRLLKDKGLL
161
LRCYTQNIDT
171
LERIAGLEQE
181
DLVEAHGTFY
191
TSHCVSASCR
201

HEYPLSWMKE
211
KIFSEVTPKC
221
EDCQSLVKPD
231
IVFFGESLPA
241
RFFSCMQSDF
251

LKVDLLLVMG
261
TSLQVQPFAS
271
LISKAPLSTP
281
RLLINKEKAG
291
QSDPFLGGGM
307

DFDSKKAYRD
317
VAWLGECDQG
327
CLALAELLGW
337
KKELEDLVRR
347
EHASIDAQ
Residue
Distance (Å)
GLY84
3.147
ALA85
2.732
GLY86
3.318
SER88
3.736
THR89
3.045
SER90
4.764
ILE93
3.732
PRO94
3.352
ASP95
3.001
PHE96
2.950
ARG97
2.775
SER98
4.181
LEU103
4.517
GLN167
2.563
ASN168
3.161
ILE169
2.787
Residue
Distance (Å)
ASP170
2.728
HIS187
3.037
PHE235
4.862
GLY261
3.190
THR262
2.994
SER263
2.799
LEU264
4.050
VAL266
3.784
ILE285
4.963
ASN286
2.766
LYS287
2.929
GLU288
3.132
GLY322
3.107
GLU323
3.268
CYS324
3.016
References  Top
REF 1 Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study. J Med Chem. 2016 Feb 25;59(4):1599-612.
REF 2 Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 2015 Feb 12;6:6263.
REF 3 Sirtuin 2 protein with H3K18 myristoylated peptide

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