Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T28887 | Target Info | |||
| Target Name | Histone deacetylase 8 (HDAC8) | ||||
| Synonyms | Histone deacetylase-8; HDACL1; HD8; CDA07 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | HDAC8 | ||||
| Biochemical Class | Carbon-nitrogen hydrolase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Vorinostat | Ligand Info | |||||
| Structure Description | Crystal structure of human histone deacetylase 8 (HDAC8) I45T mutation complexed with SAHA | PDB:7JVU | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | Yes | [1] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LTEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVVI
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: JNJ-26481585 | Ligand Info | |||||
| Structure Description | Crystal structure of a human HDAC8 L6 loop mutant complexed with Quisinostat | PDB:6HSK | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTISGDR 273 LGCFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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| Ligand Name: Trichostatin A | Ligand Info | |||||
| Structure Description | Crystal Structure of human HDAC8 complexed with Trichostatin A | PDB:1T64 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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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 .TSN or .TSN2 or .TSN3 or :3TSN;style chemicals stick;color identity;select .A:34 or .A:35 or .A:37 or .A:100 or .A:101 or .A:111 or .A:141 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:273 or .A:274 or .A:304 or .A:305 or .A:306 or .A:308; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE34
3.621
PRO35
3.300
ARG37
3.745
TYR100
3.234
ASP101
3.858
TYR111
3.263
TRP141
3.360
HIS142
2.766
HIS143
2.700
GLY151
3.577
PHE152
3.354
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: N-hydroxy-4-(naphthalen-1-yl)benzamide | Ligand Info | |||||
| Structure Description | HDAC8 Complexed with a Hydroxamic Acid | PDB:5FCW | ||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [4] |
| PDB Sequence |
SLVPVYIYSP
22 EYVSMCDSLA32 KIPKRASMVH42 SLIEAYALHK52 QMRIVKPKVA62 SMEEMATFHT 72 DAYLQHLQKV82 SQEGDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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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 .5YA or .5YA2 or .5YA3 or :35YA;style chemicals stick;color identity;select .A:100 or .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Droxinostat | Ligand Info | |||||
| Structure Description | Crystal structure of S39E HDAC8 in complex with Droxinostat | PDB:5BWZ | ||||
| Method | X-ray diffraction | Resolution | 1.59 Å | Mutation | Yes | [5] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRAEMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEHPDSIEYG97 LGYDCPATEG107 IFDYAAAIGG117 ATITAAQCLI 127 DGMCKVAINW137 SGGWHHAKKD147 EASGFCYLND157 AVLGILRLRR167 KFERILYVDL 177 DLHHGDGVED187 AFSFTSKVMT197 VSLHKFSPGF207 FPGTGDVSDV217 GLGKGRYYSV 227 NVPIQDGIQD237 EKYYQICESV247 LKEVYQAFNP257 KAVVLQLGAD267 TIAGDPMCSF 277 NMTPVGIGKC287 LKYILQWQLA297 TLILGGGGYN307 LANTARCWTY317 LTGVILGKTL 327 SSEIPDHEFF337 TAYGPDYVLE347 ITPSCRPDRN357 EPHRIQQILN367 YIKGNLKHVV 377 I
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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 .XCH or .XCH2 or .XCH3 or :3XCH;style chemicals stick;color identity;select .A:100 or .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 7-amino-4-methyl-chromen-2-one | Ligand Info | |||||
| Structure Description | Crystal structure of A188T/Y306F HDAC8 in complex with a tetrapeptide substrate | PDB:4QA5 | ||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | Yes | [6] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDTFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGFNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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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 .MCM or .MCM2 or .MCM3 or :3MCM;style chemicals stick;color identity;select .A:33 or .A:100 or .A:101 or .A:152 or .A:274; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5-(4-Methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide-4'-hydroxyamide | Ligand Info | |||||
| Structure Description | Crystal Structure of Human HDAC8 complexed with CRA-19156 | PDB:1VKG | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [3] |
| PDB Sequence |
VPVYIYSPEY
24 VSMCDSLAKI34 PKRASMVHSL44 IEAYALHKQM54 RIVKPKVASM64 EEMATFHTDA 74 YLQHLQKVSQ84 EGDDATEGIF109 DYAAAIGGAT119 ITAAQCLIDG129 MCKVAINWSG 139 GWHHAKKDEA149 SGFCYLNDAV159 LGILRLRRKF169 ERILYVDLDL179 HHGDGVEDAF 189 SFTSKVMTVS199 LHKFSPGFFP209 GTGDVSDVGL219 GKGRYYSVNV229 PIQDGIQDEK 239 YYQICESVLK249 EVYQAFNPKA259 VVLQLGADTI269 AGDPMCSFNM279 TPVGIGKCLK 289 YILQWQLATL299 ILGGGGYNLA309 NTARCWTYLT319 GVILGKTLSS329 EIPDHEFFTA 339 YGPDYVLEIT349 PSCRPDRNEP359 HRIQQILNYI369 KGNLKHVV
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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 .CRI or .CRI2 or .CRI3 or :3CRI;style chemicals stick;color identity;select .A:141 or .A:142 or .A:143 or .A:151 or .A:152 or .A:153 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-Hydroxy-4-(methyl{[5-(2-pyridinyl)-2-thienyl]sulfonyl}amino)benzamide | Ligand Info | |||||
| Structure Description | Crystal structure of inhibited human HDAC8 | PDB:1W22 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [7] |
| PDB Sequence |
SLVPVYIYSP
22 EYVSMCDSLA32 KIPKRASMVH42 SLIEAYALHK52 QMRIVKPKVA62 SMEEMATFHT 72 DAYLQHLQKV82 SQEYGLGYDC102 PATEGIFDYA112 AAIGGATITA122 AQCLIDGMCK 132 VAINWSGGWH142 HAKKDEASGF152 CYLNDAVLGI162 LRLRRKFERI172 LYVDLDLHHG 182 DGVEDAFSFT192 SKVMTVSLHK202 FSPGFFPGTG212 DVSDVGLGKG222 RYYSVNVPIQ 232 DGIQDEKYYQ242 ICESVLKEVY252 QAFNPKAVVL262 QLGADTIAGD272 PMCSFNMTPV 282 GIGKCLKYIL292 QWQLATLILG302 GGGYNLANTA312 RCWTYLTGVI322 LGKTLSSEIP 332 DHEFFTAYGP342 DYVLEITPSC352 RPDRNEPHRI362 QQILNYIKGN372 LKH |
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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 .NHB or .NHB2 or .NHB3 or :3NHB;style chemicals stick;color identity;select .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2r)-2-Amino-3-(3-Chlorophenyl)-1-[4-(2,5-Difluorobenzoyl)piperazin-1-Yl]propan-1-One | Ligand Info | |||||
| Structure Description | Crystal Structure of Human HDAC8 Inhibitor Complex, an Amino Acid Derived Inhibitor | PDB:3SFF | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [8] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 GIFDYAAAIG116 GATITAAQCL126 IDGMCKVAIN136 WSGGWHHAKK 146 DEASGFCYLN156 DAVLGILRLR166 RKFERILYVD176 LDLHHGDGVE186 DAFSFTSKVM 196 TVSLHKFSPG206 FFPGTGDVSD216 VGLGKGRYYS226 VNVPIQDGIQ236 DEKYYQICES 246 VLKEVYQAFN256 PKAVVLQLGA266 DTIAGDPMCS276 FNMTPVGIGK286 CLKYILQWQL 296 ATLILGGGGY306 NLANTARCWT316 YLTGVILGKT326 LSSEIPDHEF336 FTAYGPDYVL 346 EITPSCRPDR356 NEPHRIQQIL366 NYIKGNLKHV376 V
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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 .0DI or .0DI2 or .0DI3 or :30DI;style chemicals stick;color identity;select .A:34 or .A:37 or .A:139 or .A:140 or .A:141 or .A:142 or .A:143 or .A:150 or .A:151 or .A:152 or .A:153 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:274 or .A:303 or .A:304 or .A:305 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE34
3.765
ARG37
4.107
GLY139
4.513
GLY140
3.390
TRP141
3.443
HIS142
2.897
HIS143
3.392
SER150
4.523
GLY151
3.205
PHE152
3.628
CYS153
3.801
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| Ligand Name: (2r)-2-Amino-3-(2,4-Dichlorophenyl)-1-(1,3-Dihydro-2h-Isoindol-2-Yl)propan-1-One | Ligand Info | |||||
| Structure Description | Crystal Structure of Human HDAC8 Inhibitor Complex, an Amino Acid Derived Inhibitor | PDB:3SFH | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [8] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QGIFDYAAAI115 GGATITAAQC125 LIDGMCKVAI135 NWSGGWHHAK 145 KDEASGFCYL155 NDAVLGILRL165 RRKFERILYV175 DLDLHHGDGV185 EDAFSFTSKV 195 MTVSLHKFSP205 GFFPGTGDVS215 DVGLGKGRYY225 SVNVPIQDGI235 QDEKYYQICE 245 SVLKEVYQAF255 NPKAVVLQLG265 ADTIAGDPMC275 SFNMTPVGIG285 KCLKYILQWQ 295 LATLILGGGG305 YNLANTARCW315 TYLTGVILGK325 TLSSEIPDHE335 FFTAYGPDYV 345 LEITPSCRPD355 RNEPHRIQQI365 LNYIKGNLKH375 VV
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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 .1DI or .1DI2 or .1DI3 or :31DI;style chemicals stick;color identity;select .A:34 or .A:37 or .A:140 or .A:141 or .A:142 or .A:143 or .A:151 or .A:152 or .A:153 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:274 or .A:303 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-(Dimethylamino)-n-[7-(hydroxyamino)-7-oxoheptyl]benzamide | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of human HDAC8 D101L variant | PDB:3EW8 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [9] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGEYGLGYL101 CPATEGIFDY111 AAAIGGATIT121 AAQCLIDGMC 131 KVAINWSGGW141 HHAKKDEASG151 FCYLNDAVLG161 ILRLRRKFER171 ILYVDLDLHH 181 GDGVEDAFSF191 TSKVMTVSLH201 KFSPGFFPGT211 GDVSDVGLGK221 GRYYSVNVPI 231 QDGIQDEKYY241 QICESVLKEV251 YQAFNPKAVV261 LQLGADTIAG271 DPMCSFNMTP 281 VGIGKCLKYI291 LQWQLATLIL301 GGGGYNLANT311 ARCWTYLTGV321 ILGKTLSSEI 331 PDHEFFTAYG341 PDYVLEITPS351 CRPDRNEPHR361 IQQILNYIKG371 NLKHVVI |
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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 .B3N or .B3N2 or .B3N3 or :3B3N;style chemicals stick;color identity;select .A:100 or .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:305 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (2r)-N~8~-Hydroxy-2-{[(5-Methoxy-2-Methyl-1h-Indol-3-Yl)acetyl]amino}-N~1~-[2-(2-Phenyl-1h-Indol-3-Yl)ethyl]octanediamide | Ligand Info | |||||
| Structure Description | Crystal structure of HDAC8-inhibitor complex | PDB:2V5X | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [10] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRADMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHV
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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 .V5X or .V5X2 or .V5X3 or :3V5X;style chemicals stick;color identity;select .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:206 or .A:207 or .A:208 or .A:209 or .A:210 or .A:263 or .A:267 or .A:273 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2E)-N-hydroxy-3-[1-methyl-4-(phenylacetyl)-1H-pyrrol-2-yl]prop-2-enamide | Ligand Info | |||||
| Structure Description | Crystal Structure Analysis of Human HDAC8 complexed with APHA in a new monoclinic crystal form | PDB:3F07 | ||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | No | [9] |
| PDB Sequence |
SLVPVYIYSP
22 EYVSMCDSLA32 KIPKRASMVH42 SLIEAYALHK52 QMRIVKPKVA62 SMEEMATFHT 72 DAYLQHLQKV82 SQEGDDDHPD92 SIEYGLGYDC102 PATEGIFDYA112 AAIGGATITA 122 AQCLIDGMCK132 VAINWSGGWH142 HAKKDEASGF152 CYLNDAVLGI162 LRLRRKFERI 172 LYVDLDLHHG182 DGVEDAFSFT192 SKVMTVSLHK202 FSPGFFPGTG212 DVSDVGLGKG 222 RYYSVNVPIQ232 DGIQDEKYYQ242 ICESVLKEVY252 QAFNPKAVVL262 QLGADTIAGD 272 PMCSFNMTPV282 GIGKCLKYIL292 QWQLATLILG302 GGGYNLANTA312 RCWTYLTGVI 322 LGKTLSSEIP332 DHEFFTAYGP342 DYVLEITPSC352 RPDRNEPHRI362 QQILNYIKGN 372 LKHVVI
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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 .AGE or .AGE2 or .AGE3 or :3AGE;style chemicals stick;color identity;select .A:33 or .A:101 or .A:140 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:206 or .A:207 or .A:208 or .A:263 or .A:267 or .A:274 or .A:303 or .A:304 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (5r,8s,11s)-5-Methyl-8-(Propan-2-Yl)-11-[(1e)-4-Sulfanylbut-1-En-1-Yl]-3,17-Dithia-7,10,14,19,20-Pentaazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-Triene-6,9,13-Trione | Ligand Info | |||||
| Structure Description | Crystal structure of S39D HDAC8 in complex with a largazole analogue. | PDB:4RN0 | ||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | Yes | [11] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRADMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGSIEYGLG99 YDCPATEGIF109 DYAAAIGGAT119 ITAAQCLIDG 129 MCKVAINWSG139 GWHHAKKDEA149 SGFCYLNDAV159 LGILRLRRKF169 ERILYVDLDL 179 HHGDGVEDAF189 SFTSKVMTVS199 LHKFSPGFFP209 GTGDVSDVGL219 GKGRYYSVNV 229 PIQDGIQDEK239 YYQICESVLK249 EVYQAFNPKA259 VVLQLGADTI269 AGDPMCSFNM 279 TPVGIGKCLK289 YILQWQLATL299 ILGGGGYNLA309 NTARCWTYLT319 GVILGKTLSS 329 EIPDHEFFTA339 YGPDYVLEIT349 PSCRPDRNEP359 HRIQQILNYI369 KGNLKHVVI |
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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 .L6G or .L6G2 or .L6G3 or :3L6G;style chemicals stick;color identity;select .A:100 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N6-Acetyl-L-lysine | Ligand Info | |||||
| Structure Description | Crystal structure of A188T/Y306F HDAC8 in complex with a tetrapeptide substrate | PDB:4QA5 | ||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | Yes | [6] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDTFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGFNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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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 .ALY or .ALY2 or .ALY3 or :3ALY;style chemicals stick;color identity;select .A:100 or .A:101 or .A:141 or .A:142 or .A:143 or .A:151 or .A:152 or .A:153 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:303 or .A:304 or .A:305 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (5r,8s,11s)-5-Methyl-8-(Propan-2-Yl)-11-[(1e)-4-Sulfanylbut-1-En-1-Yl]-3-Thia-7,10,14,20,21-Pentaazatricyclo[14.3.1.1~2,5~]henicosa-1(20),2(21),16,18-Tetraene-6,9,13-Trione | Ligand Info | |||||
| Structure Description | Crystal structure of S39D HDAC8 in complex with a largazole analogue. | PDB:4RN1 | ||||
| Method | X-ray diffraction | Resolution | 2.18 Å | Mutation | Yes | [11] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRADMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDSIEYG97 LGYDCPATEG107 IFDYAAAIGG117 ATITAAQCLI 127 DGMCKVAINW137 SGGWHHAKKD147 EASGFCYLND157 AVLGILRLRR167 KFERILYVDL 177 DLHHGDGVED187 AFSFTSKVMT197 VSLHKFSPGF207 FPGTGDVSDV217 GLGKGRYYSV 227 NVPIQDGIQD237 EKYYQICESV247 LKEVYQAFNP257 KAVVLQLGAD267 TIAGDPMCSF 277 NMTPVGIGKC287 LKYILQWQLA297 TLILGGGGYN307 LANTARCWTY317 LTGVILGKTL 327 SSEIPDHEFF337 TAYGPDYVLE347 ITPSCRPDRN357 EPHRIQQILN367 YIKGNLKHVV 377 I
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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 .L8G or .L8G2 or .L8G3 or :3L8G;style chemicals stick;color identity;select .A:100 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (5r,8s,11s)-5-Methyl-8-(Propan-2-Yl)-11-[(1e)-4-Sulfanylbut-1-En-1-Yl]-3-Thia-7,10,14,17,21-Pentaazatricyclo[14.3.1.1~2,5~]henicosa-1(20),2(21),16,18-Tetraene-6,9,13-Trione | Ligand Info | |||||
| Structure Description | Crystal structure of S39D HDAC8 in complex with a largazole analogue. | PDB:4RN2 | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | Yes | [11] |
| PDB Sequence |
VPVYIYSPEY
24 VSMCDSLAKI34 PKRADMVHSL44 IEAYALHKQM54 RIVKPKVASM64 EEMATFHTDA 74 YLQHLQKVSQ84 SIEYGLTEGI108 FDYAAAIGGA118 TITAAQCLID128 GMCKVAINWS 138 GGWHHAKKDE148 ASGFCYLNDA158 VLGILRLRRK168 FERILYVDLD178 LHHGDGVEDA 188 FSFTSKVMTV198 SLHKFSPGFF208 PGTGDVSDVG218 LGKGRYYSVN228 VPIQDGIQDE 238 KYYQICESVL248 KEVYQAFNPK258 AVVLQLGADT268 IAGDPMCSFN278 MTPVGIGKCL 288 KYILQWQLAT298 LILGGGGYNL308 ANTARCWTYL318 TGVILGKTLS328 SEIPDHEFFT 338 AYGPDYVLEI348 TPSCRPDRNE358 PHRIQQILNY368 IKGNLKHVV
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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 .L7G or .L7G2 or .L7G3 or :3L7G;style chemicals stick;color identity;select .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:267 or .A:274 or .A:304 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-{2-[(1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl]phenyl}-2-phenoxybenzamide | Ligand Info | |||||
| Structure Description | Crystal structure of HDAC8 in complex with compound 3 | PDB:6ODB | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [12] |
| PDB Sequence |
SLVPVYIYSP
22 EYVSMCDSLA32 KIPKRASMVH42 SLIEAYALHK52 QMRIVKPKVA62 SMEEMATFHT 72 DAYLQHLQKV82 SQEGDDDHPD92 SIEYGLGYDC102 PATEGIFDYA112 AAIGGATITA 122 AQCLIDGMCK132 VAINWSGGWH142 HAKKDEASGF152 CYLNDAVLGI162 LRLRRKFERI 172 LYVDLDLHHG182 DGVEDAFSFT192 SKVMTVSLHK202 FSPGFFPGTG212 DVSDVGLGKG 222 RYYSVNVPIQ232 DGIQDEKYYQ242 ICESVLKEVY252 QAFNPKAVVL262 QLGADTIAGD 272 PMCSFNMTPV282 GIGKCLKYIL292 QWQLATLILG302 GGGYNLANTA312 RCWTYLTGVI 322 LGKTLSSEIP332 DHEFFTAYGP342 DYVLEITPSC352 RPDRNEPHRI362 QQILNYIKGN 372 LKHVV
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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 .M8G or .M8G2 or .M8G3 or :3M8G;style chemicals stick;color identity;select .A:33 or .A:34 or .A:100 or .A:101 or .A:103 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:273 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2E)-3-[2-(3-cyclopentyl-5,5-dimethyl-2-oxoimidazolidin-1-yl)phenyl]-N-hydroxyprop-2-enamide | Ligand Info | |||||
| Structure Description | Crystal structure of HDAC8 in complex with compound 30 | PDB:6ODC | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [13] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVVIEG
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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 .M7Y or .M7Y2 or .M7Y3 or :3M7Y;style chemicals stick;color identity;select .A:33 or .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:273 or .A:274 or .A:303 or .A:304 or .A:306; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-{2-[3-(hydroxyamino)-3-oxopropyl]phenyl}-3-(trifluoromethyl)benzamide | Ligand Info | |||||
| Structure Description | Crystal structure of HDAC8 in complex with compound 2 | PDB:6ODA | ||||
| Method | X-ray diffraction | Resolution | 2.88 Å | Mutation | No | [14] |
| PDB Sequence |
LVPVYIYSPE
23 YVSMCDSLAK33 IPKRASMVHS43 LIEAYALHKQ53 MRIVKPKVAS63 MEEMATFHTD 73 AYLQHLQKVS83 QEGDDDHPDS93 IEYGLGYDCP103 ATEGIFDYAA113 AIGGATITAA 123 QCLIDGMCKV133 AINWSGGWHH143 AKKDEASGFC153 YLNDAVLGIL163 RLRRKFERIL 173 YVDLDLHHGD183 GVEDAFSFTS193 KVMTVSLHKF203 SPGFFPGTGD213 VSDVGLGKGR 223 YYSVNVPIQD233 GIQDEKYYQI243 CESVLKEVYQ253 AFNPKAVVLQ263 LGADTIAGDP 273 MCSFNMTPVG283 IGKCLKYILQ293 WQLATLILGG303 GGYNLANTAR313 CWTYLTGVIL 323 GKTLSSEIPD333 HEFFTAYGPD343 YVLEITPSCR353 PDRNEPHRIQ363 QILNYIKGNL 373 KHVV
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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 .C7 or .C72 or .C73 or :3C7;style chemicals stick;color identity;select .A:33 or .A:101 or .A:142 or .A:143 or .A:151 or .A:152 or .A:178 or .A:180 or .A:208 or .A:263 or .A:267 or .A:273 or .A:274 or .A:304 or .A:306; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders. J Struct Biol. 2021 Mar;213(1):107681. | ||||
| REF 2 | Characterization of Histone Deacetylase 8 (HDAC8) Selective Inhibition Reveals Specific Active Site Structural and Functional Determinants. J Med Chem. 2018 Nov 21;61(22):10000-10016. | ||||
| REF 3 | Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure. 2004 Jul;12(7):1325-34. | ||||
| REF 4 | Structure of 'linkerless' hydroxamic acid inhibitor-HDAC8 complex confirms the formation of an isoform-specific subpocket. J Struct Biol. 2016 Sep;195(3):373-378. | ||||
| REF 5 | Phosphorylation of Histone Deacetylase 8: Structural and Mechanistic Analysis of the Phosphomimetic S39E Mutant. Biochemistry. 2019 Nov 12;58(45):4480-4493. | ||||
| REF 6 | Compromised structure and function of HDAC8 mutants identified in Cornelia de Lange Syndrome spectrum disorders. ACS Chem Biol. 2014 Sep 19;9(9):2157-64. | ||||
| REF 7 | Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15064-9. | ||||
| REF 8 | Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors. Bioorg Med Chem. 2011 Aug 1;19(15):4626-34. | ||||
| REF 9 | Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry. 2008 Dec 23;47(51):13554-63. | ||||
| REF 10 | Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. EMBO Rep. 2007 Sep;8(9):879-84. | ||||
| REF 11 | Variable active site loop conformations accommodate the binding of macrocyclic largazole analogues to HDAC8. Biochemistry. 2015 Mar 31;54(12):2126-35. | ||||
| REF 12 | Structure-based Discovery of Novel N-(E)-N-Hydroxy-3-(2-(2-oxoimidazolidin-1-yl)phenyl)acrylamides as Potent and Selective HDAC8 inhibitors | ||||
| REF 13 | Structure-based Discovery of Novel N-(E)-N-Hydroxy-3-(2-(2-oxoimidazolidin-1-yl)phenyl)acrylamides as Potent and Selective HDAC8 inhibitors | ||||
| REF 14 | Crystal structure of HDAC8 in complex with compound 2 | ||||
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