Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Adenosine-5-diphosphoribose | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OCC4C(C(C(O4)O)O)O)O)O)N | ||||
| InChI | 1S/C15H23N5O14P2/c16-12-7-13(18-3-17-12)20(4-19-7)14-10(23)8(21)5(32-14)1-30-35(26,27)34-36(28,29)31-2-6-9(22)11(24)15(25)33-6/h3-6,8-11,14-15,21-25H,1-2H2,(H,26,27)(H,28,29)(H2,16,17,18)/t5-,6-,8-,9-,10-,11-,14-,15+/m1/s1 | ||||
| InChIKey | SRNWOUGRCWSEMX-ZQSHOCFMSA-N | ||||
| PubChem Compound ID | 447048 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3ZGV Structure of human SIRT2 in complex with ADP-ribose | ||||||
| Method | X-ray diffraction | Resolution | 2.27 Å | Mutation | No | [1] |
| PDB Sequence |
RLLDELTLEG
66 VARYMQSERC76 RRVICLVGAG86 ISTSAGIPDF96 RSPSTGLYDN106 LEKYHLPYPE 116 AIFEISYFKK126 HPEPFFALAK136 ELYQFKPTIC148 HYFMRLLKDK158 GLLLRCYTQN 168 IDTLERIAGL178 EQEDLVEAHG188 TFYTSHCVSA198 SCRHEYPLSW208 MKEKIFSEVT 218 PKCEDCQSLV228 KPDIVFFGES238 LPARFFSCMQ248 SDFLKVDLLL258 VMGTSLQVQP 268 FASLISKAPL278 STPRLLINKE288 KAGQSDPFLG298 MIMGLGGGMD308 FDSKKAYRDV 318 AWLGECDQGC328 LALAELLGWK338 KELEDLVRRE348 HASIDAQ
|
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|
|
GLY84
2.671
ALA85
1.901
GLY86
2.551
THR89
1.951
SER90
3.148
ASP95
2.379
PHE96
2.114
ARG97
1.961
SER98
2.559
TYR104
2.040
GLU116
4.582
PHE119
4.262
GLN167
2.486
ASN168
4.093
HIS187
2.214
VAL233
4.738
|
|||||
| PDB ID: 5D7O Crystal structure of Sirt2-ADPR at an improved resolution | ||||||
| Method | X-ray diffraction | Resolution | 1.63 Å | Mutation | No | [2] |
| PDB Sequence |
RLLDELTLEG
66 VARYMQSERC76 RRVICLVGAG86 ISTSAGIPDF96 RSPSTGLYDN106 LEKYHLPYPE 116 AIFEISYFKK126 HPEPFFALAK136 ELYPGQFKPT146 ICHYFMRLLK156 DKGLLLRCYT 166 QNIDTLERIA176 GLEQEDLVEA186 HGTFYTSHCV196 SASCRHEYPL206 SWMKEKIFSE 216 VTPKCEDCQS226 LVKPDIVFFG236 ESLPARFFSC246 MQSDFLKVDL256 LLVMGTSLQV 266 QPFASLISKA276 PLSTPRLLIN286 KEKAGQSDPF296 LGMIMGLGGG306 MDFDSKKAYR 316 DVAWLGECDQ326 GCLALAELLG336 WKKELEDLVR346 REHASIDAQ
|
|||||
|
|
GLY84
3.266
ALA85
2.820
GLY86
3.306
THR89
2.945
SER90
4.705
ASP95
3.271
PHE96
2.764
ARG97
2.714
SER98
4.007
TYR104
2.721
GLN167
3.080
ASN168
4.233
HIS187
2.842
VAL233
4.991
|
|||||
| PDB ID: 5D7P Crystal structure of human Sirt2 in complex with ADPR and EX-243 | ||||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | No | [2] |
| PDB Sequence |
HMERLLDELT
63 LEGVARYMQS73 ERCRRVICLV83 GAGISTSAGI93 PDFRSPSTGL103 YDNLEKYHLP 113 YPEAIFEISY123 FKKHPEPFFA133 LAKELYPGQF143 KPTICHYFMR153 LLKDKGLLLR 163 CYTQNIDTLE173 RIAGLEQEDL183 VEAHGTFYTS193 HCVSASCRHE203 YPLSWMKEKI 213 FSEVTPKCED223 CQSLVKPDIV233 FFGESLPARF243 FSCMQSDFLK253 VDLLLVMGTS 263 LQVQPFASLI273 SKAPLSTPRL283 LINKEKAGQS293 DPFLGMIMGL303 GGGMDFDSKK 313 AYRDVAWLGE323 CDQGCLALAE333 LLGWKKELED343 LVRREHASID353 AQ |
|||||
|
|
GLY84
3.259
ALA85
2.816
GLY86
3.239
THR89
2.891
SER90
4.574
ASP95
3.210
PHE96
2.806
ARG97
2.765
SER98
3.942
TYR104
2.843
GLN167
3.030
ASN168
4.313
HIS187
2.823
VAL233
4.689
|
|||||
| PDB ID: 4RMJ Human Sirt2 in complex with ADP ribose and nicotinamide | ||||||
| Method | X-ray diffraction | Resolution | 1.87 Å | Mutation | No | [3] |
| PDB Sequence |
MERLLDELTL
64 EGVARYMQSE74 RCRRVICLVG84 AGISTSAGIP94 DFRSPSTGLY104 DNLEKYHLPY 114 PEAIFEISYF124 KKHPEPFFAL134 AKELYPGQFK144 PTICHYFMRL154 LKDKGLLLRC 164 YTQNIDTLER174 IAGLEQEDLV184 EAHGTFYTSH194 CVSASCRHEY204 PLSWMKEKIF 214 SEVTPKCEDC224 QSLVKPDIVF234 FGESLPARFF244 SCMQSDFLKV254 DLLLVMGTSL 264 QVQPFASLIS274 KAPLSTPRLL284 INKEKAGQSD294 PFLGMIMGLG304 GGMDFDSKKA 314 YRDVAWLGEC324 DQGCLALAEL334 LGWKKELEDL344 VRREHASIDA354 Q |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AR6 or .AR62 or .AR63 or :3AR6;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:89 or .A:90 or .A:95 or .A:96 or .A:97 or .A:98 or .A:104 or .A:167 or .A:168 or .A:187 or .A:233 or .A:235 or .A:261 or .A:262 or .A:263 or .A:264 or .A:266 or .A:285 or .A:286 or .A:287 or .A:288 or .A:322 or .A:323 or .A:324; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.264
ALA85
2.830
GLY86
3.263
THR89
2.961
SER90
4.649
ASP95
3.212
PHE96
2.837
ARG97
2.723
SER98
3.837
TYR104
2.771
GLN167
2.960
ASN168
4.117
HIS187
2.668
VAL233
4.909
|
|||||
| PDB ID: 5D7Q Crystal structure of human Sirt2 in complex with ADPR and CHIC35 | ||||||
| Method | X-ray diffraction | Resolution | 2.01 Å | Mutation | No | [2] |
| PDB Sequence |
HMERLLDELT
63 LEGVARYMQS73 ERCRRVICLV83 GAGISTSAGI93 PDFRSPSTGL103 YDNLEKYHLP 113 YPEAIFEISY123 FKKHPEPFFA133 LAKELYPGQF143 KPTICHYFMR153 LLKDKGLLLR 163 CYTQNIDTLE173 RIAGLEQEDL183 VEAHGTFYTS193 HCVSASCRHE203 YPLSWMKEKI 213 FSEVTPKCED223 CQSLVKPDIV233 FFGESLPARF243 FSCMQSDFLK253 VDLLLVMGTS 263 LQVQPFASLI273 SKAPLSTPRL283 LINKEKAGQS293 DPFLGMIMGL303 GGGMDFDSKK 313 AYRDVAWLGE323 CDQGCLALAE333 LLGWKKELED343 LVRREHASID353 A |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AR6 or .AR62 or .AR63 or :3AR6;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:89 or .A:90 or .A:95 or .A:96 or .A:97 or .A:98 or .A:104 or .A:167 or .A:168 or .A:187 or .A:233 or .A:235 or .A:261 or .A:262 or .A:263 or .A:264 or .A:266 or .A:285 or .A:286 or .A:287 or .A:288 or .A:322 or .A:323 or .A:324; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.310
ALA85
2.826
GLY86
3.342
THR89
2.839
SER90
4.556
ASP95
3.278
PHE96
2.781
ARG97
2.703
SER98
3.936
TYR104
2.825
GLN167
2.978
ASN168
4.225
HIS187
2.728
VAL233
4.690
|
|||||
| PDB ID: 6QCN Human Sirt2 in complex with ADP-ribose and the inhibitor quercetin | ||||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | No | [4] |
| PDB Sequence |
RLLDELTLEG
66 VARYMQSERC76 RRVICLVGAG86 ISTSAGIPDF96 RSPSTGLYDN106 LEKYHLPYPE 116 AIFEISYFKK126 HPEPFFALAK136 ELYPGQFKPT146 ICHYFMRLLK156 DKGLLLRCYT 166 QNIDTLERIA176 GLEQEDLVEA186 HGTFYTSHCV196 SASCRHEYPL206 SWMKEKIFSE 216 VTPKCEDCQS226 LVKPDIVFFG236 ESLPARFFSC246 MQSDFLKVDL256 LLVMGTSLQV 266 QPFASLISKA276 PLSTPRLLIN286 KEKAGQSDPF296 LGMIMGLGGG306 MDFDSKKAYR 316 DVAWLGECDQ326 GCLALAELLG336 WKKELEDLVR346 REHASIDAQ
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AR6 or .AR62 or .AR63 or :3AR6;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:89 or .A:90 or .A:95 or .A:96 or .A:97 or .A:98 or .A:104 or .A:119 or .A:167 or .A:168 or .A:187 or .A:233 or .A:235 or .A:261 or .A:262 or .A:263 or .A:264 or .A:266 or .A:285 or .A:286 or .A:287 or .A:288 or .A:322 or .A:323 or .A:324; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
3.385
ALA85
2.769
GLY86
3.499
THR89
2.674
SER90
4.755
ASP95
3.233
PHE96
2.802
ARG97
2.843
SER98
4.014
TYR104
2.622
PHE119
4.882
GLN167
2.883
ASN168
4.376
HIS187
2.590
|
|||||
| PDB ID: 5MAR Structure of human SIRT2 in complex with 1,2,4-Oxadiazole inhibitor and ADP ribose. | ||||||
| Method | X-ray diffraction | Resolution | 1.89 Å | Mutation | No | [5] |
| PDB Sequence |
HMERLLDELT
63 LEGVARYMQS73 ERCRRVICLV83 GAGISTSAGI93 PDFRSPSTGL103 YDNLEKYHLP 113 YPEAIFEISY123 FKKHPEPFFA133 LAKELYPGQF143 KPTICHYFMR153 LLKDKGLLLR 163 CYTQNIDTLE173 RIAGLEQEDL183 VEAHGTFYTS193 HCVSASCRHE203 YPLSWMKEKI 213 FSEVTPKCED223 CQSLVKPDIV233 FFGESLPARF243 FSCMQSDFLK253 VDLLLVMGTS 263 LQVQPFASLI273 SKAPLSTPRL283 LINKEKAGQS293 DPFLGMIMGL303 GGGMDFDSKK 313 AYRDVAWLGE323 CDQGCLALAE333 LLGWKKELED343 LVRREHASID353 AQ |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AR6 or .AR62 or .AR63 or :3AR6;style chemicals stick;color identity;select .A:84 or .A:85 or .A:86 or .A:87 or .A:89 or .A:90 or .A:95 or .A:96 or .A:97 or .A:98 or .A:104 or .A:116 or .A:119 or .A:167 or .A:168 or .A:187 or .A:233 or .A:235 or .A:261 or .A:262 or .A:263 or .A:264 or .A:265 or .A:266 or .A:285 or .A:286 or .A:287 or .A:288 or .A:290 or .A:322 or .A:323 or .A:324 or .A:325; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY84
2.583
ALA85
2.103
GLY86
2.508
ILE87
4.755
THR89
2.472
SER90
3.350
ASP95
2.350
PHE96
2.028
ARG97
1.893
SER98
2.640
TYR104
1.944
GLU116
4.186
PHE119
4.369
GLN167
2.801
ASN168
4.239
HIS187
1.906
VAL233
4.613
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structure analysis of human Sirt2 and its ADP-ribose complex. J Struct Biol. 2013 May;182(2):136-43. | ||||
| REF 2 | Seeding for sirtuins: microseed matrix seeding to obtain crystals of human Sirt3 and Sirt2 suitable for soaking. Acta Crystallogr F Struct Biol Commun. 2015 Dec;71(Pt 12):1498-510. | ||||
| REF 3 | Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 2015 Feb 12;6:6263. | ||||
| REF 4 | Structural basis for the activation and inhibition of Sirtuin 6 by quercetin and its derivatives. Sci Rep. 2019 Dec 16;9(1):19176. | ||||
| REF 5 | Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure-Activity Relationship, X-ray Crystal Structure, and Anticancer Activity. J Med Chem. 2017 Mar 23;60(6):2344-2360. | ||||
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