Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T17967 | Target Info | |||
| Target Name | Pyruvate dehydrogenase kinase 2 (PDHK2) | ||||
| Synonyms | PDKII; PDK2; PDH kinase 2; [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | PDK2 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | N-(2-Aminoethyl)-2-{3-chloro-4-[(4-isopropylbenzyl)oxy]phenyl} acetamide | Ligand Info | |||
| Canonical SMILES | CC(C)C1=CC=C(C=C1)COC2=C(C=C(C=C2)CC(=O)NCCN)Cl | ||||
| InChI | 1S/C20H25ClN2O2/c1-14(2)17-6-3-15(4-7-17)13-25-19-8-5-16(11-18(19)21)12-20(24)23-10-9-22/h3-8,11,14H,9-10,12-13,22H2,1-2H3,(H,23,24) | ||||
| InChIKey | DFXJYVQAAFOZDP-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 6102763 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4V26 VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context- dependent cytostasis in cancer cells | ||||||
| Method | X-ray diffraction | Resolution | 2.49 Å | Mutation | No | [1] |
| PDB Sequence |
ASAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGSNA36 CEKTSFTFLR46 QELPVRLANI56 MKEINLLPDR 66 VLSTPSVQLV76 QSWYVQSLLD86 IMEFLDKDPE96 DHRTLSQFTD106 ALVTIRNRHN 116 DVVPTMAQGV126 LEYKDTYGDD136 PVSNQNIQYF146 LDRFYLSRIS156 IRMLINQHTL 166 IFDPKHIGSI183 DPNCNVSEVV193 KDAYDMAKLL203 CDKYYMASPD213 LEIQEINAAN 223 SKQPIHMVYV233 PSHLYHMLFE243 LFKNAMRATV253 ESHESSLILP263 PIKVMVALGE 273 EDLSIKMSDR283 GGGVPLRKIE293 RLFSYMYSTA303 PPLAGFGYGL322 PISRLYAKYF 332 QGDLQLFSME342 GFGTDAVIYL352 KALSTDSVER362 LPVY
|
|||||
|
|
||||||
| PDB ID: 5M4P Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGSNA36 CEKTSFTFLR46 QELPVRLANI56 MKEINLLPDR 66 VLSTPSVQLV76 QSWYVQSLLD86 IMEFLDKDPE96 DHRTLSQFTD106 ALVTIRNRHN 116 DVVPTMAQGV126 LEYKDTYGDD136 PVSNQNIQYF146 LDRFYLSRIS156 IRMLINQHTL 166 IFDPKHIGSI183 DPNCNVSEVV193 KDAYDMAKLL203 CDKYYMASPD213 LEIQEINAAN 223 SKQPIHMVYV233 PSHLYHMLFE243 LFKNAMRATV253 ESHESSLILP263 PIKVMVALGE 273 EDLSIKMSDR283 GGGVPLRKIE293 RLFSYMYSTA303 PLAGFGYGLP323 ISRLYAKYFQ 333 GDLQLFSMEG343 FGTDAVIYLK353 ALSTDSVERL363 PVY
|
|||||
|
|
||||||
| PDB ID: 5M4M Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGSNA36 CEKTSFTFLR46 QELPVRLANI56 MKEINLLPDR 66 VLSTPSVQLV76 QSWYVQSLLD86 IMEFLDKDPE96 DHRTLSQFTD106 ALVTIRNRHN 116 DVVPTMAQGV126 LEYKDTYGDD136 PVSNQNIQYF146 LDRFYLSRIS156 IRMLINQHTL 166 IFDPKHIGSI183 DPNCNVSEVV193 KDAYDMAKLL203 CDKYYMASPD213 LEIQEINAAN 223 SKQPIHMVYV233 PSHLYHMLFE243 LFKNAMRATV253 ESHESSLILP263 PIKVMVALGE 273 EDLSIKMSDR283 GGGVPLRKIE293 RLFSYMYSTA303 PPLAGFGYGL322 PISRLYAKYF 332 QGDLQLFSME342 GFGTDAVIYL352 KALSTDSVER362 LPVY
|
|||||
|
|
||||||
| PDB ID: 4V25 VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context- dependent cytostasis in cancer cells | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [1] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGSAC37 EKTSFTFLRQ47 ELPVRLANIM57 KEINLLPDRV 67 LSTPSVQLVQ77 SWYVQSLLDI87 MEFLDKDPED97 HRTLSQFTDA107 LVTIRNRHND 117 VVPTMAQGVL127 EYKDTYGDDP137 VSNQNIQYFL147 DRFYLSRISI157 RMLINQHTLI 167 FDPKHIGSID184 PNCNVSEVVK194 DAYDMAKLLC204 DKYYMASPDL214 EIQEINAANS 224 KQPIHMVYVP234 SHLYHMLFEL244 FKNAMRATVE254 SHESSLILPP264 IKVMVALGEE 274 DLSIKMSDRG284 GGVPLRKIER294 LFSYMYSTAP304 PLAGFGYGLP323 ISRLYAKYFQ 333 GDLQLFSMEG343 FGTDAVIYLK353 ALSTDSVERL363 PVY
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TF3 or .TF32 or .TF33 or :3TF3;style chemicals stick;color identity;select .A:63 or .A:64 or .A:66 or .A:67 or .A:73 or .A:122 or .A:125 or .A:126 or .A:129 or .A:138 or .A:139 or .A:142 or .A:143 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 5M4K Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [2] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFNACE38 KTSFTFLRQE48 LPVRLANIMK58 EINLLPDRVL 68 STPSVQLVQS78 WYVQSLLDIM88 EFLDKDPEDH98 RTLSQFTDAL108 VTIRNRHNDV 118 VPTMAQGVLE128 YKDTYGDDPV138 SNQNIQYFLD148 RFYLSRISIR158 MLINQHTLIF 168 DPKHIGSIDP185 NCNVSEVVKD195 AYDMAKLLCD205 KYYMASPDLE215 IQEINAANSK 225 QPIHMVYVPS235 HLYHMLFELF245 KNAMRATVES255 HESSLILPPI265 KVMVALGEED 275 LSIKMSDRGG285 GVPLRKIERL295 FSYMYSTAPY320 GLPISRLYAK330 YFQGDLQLFS 340 MEGFGTDAVI350 YLKALSTDSV360 ERLPVY
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TF3 or .TF32 or .TF33 or :3TF3;style chemicals stick;color identity;select .A:63 or .A:64 or .A:66 or .A:67 or .A:73 or .A:122 or .A:125 or .A:126 or .A:129 or .A:138 or .A:139 or .A:142 or .A:143 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 5M4N Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [2] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGACE38 KTSFTFLRQE48 LPVRLANIMK58 EINLLPDRVL 68 STPSVQLVQS78 WYVQSLLDIM88 EFLDKDPEDH98 RTLSQFTDAL108 VTIRNRHNDV 118 VPTMAQGVLE128 YKDTYGDDPV138 SNQNIQYFLD148 RFYLSRISIR158 MLINQHTLIF 168 DPKHIGSIDP185 NCNVSEVVKD195 AYDMAKLLCD205 KYYMASPDLE215 IQEINAANSK 225 QPIHMVYVPS235 HLYHMLFELF245 KNAMRATVES255 HESSLILPPI265 KVMVALGEED 275 LSIKMSDRGG285 GVPLRKIERL295 FSYMYSTAPY320 GLPISRLYAK330 YFQGDLQLFS 340 MEGFGTDAVI350 YLKALSTDSV360 ERLPVY
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TF3 or .TF32 or .TF33 or :3TF3;style chemicals stick;color identity;select .A:63 or .A:64 or .A:66 or .A:67 or .A:73 or .A:122 or .A:125 or .A:126 or .A:129 or .A:138 or .A:139 or .A:142 or .A:143 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 2BU7 crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
GSAPKYIEHF
15 SKFSPSPLSM25 KQFLDFGSSN35 ACEKTSFTFL45 RQELPVRLAN55 IMKEINLLPD 65 RVLSTPSVQL75 VQSWYVQSLL85 DIMEFLDKDP95 EDHRTLSQFT105 DALVTIRNRH 115 NDVVPTMAQG125 VLEYKDTYGD135 DPVSNQNIQY145 FLDRFYLSRI155 SIRMLINQHT 165 LIFDPKHIGS182 IDPNCNVSEV192 VKDAYDMAKL202 LCDKYYMASP212 DLEIQEINAA 222 NSKQPIHMVY232 VPSHLYHMLF242 ELFKNAMRAT252 VESHESSLIL262 PPIKVMVALG 272 EEDLSIKMSD282 RGGGVPLRKI292 ERLFSYMYST302 APGYGLPISR326 LYAKYFQGDL 336 QLFSMEGFGT346 DAVIYLKALS356 TDSVERLPVY366 NKSAWRHYQT376 IQEAGDWCV |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TF3 or .TF32 or .TF33 or :3TF3;style chemicals stick;color identity;select .A:63 or .A:64 or .A:66 or .A:67 or .A:72 or .A:73 or .A:122 or .A:125 or .A:126 or .A:129 or .A:138 or .A:139 or .A:142 or .A:143 or .A:146 or .A:147 or .A:374 or .A:376; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. Oncotarget. 2014 Dec 30;5(24):12862-76. | ||||
| REF 2 | Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase. J Med Chem. 2017 Mar 23;60(6):2271-2286. | ||||
| REF 3 | Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands. Biochemistry. 2006 Jan 17;45(2):402-15. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.