Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T77594 | Target Info | |||
| Target Name | Endoplasmic reticulum chaperone BiP (HSPA5) | ||||
| Synonyms | Immunoglobulin heavy chainbinding protein; Immunoglobulin heavy chain-binding protein; Heat shock protein family A member 5; Heat shock protein 70 family protein 5; Heat shock 70 kDa protein 5; HSP70 family protein 5; GRP78; GRP-78; Endoplasmic reticulum lumenal Ca(2+)binding protein grp78; Binding-immunoglobulin protein; BiP; 78 kDa glucose-regulated protein | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | HSPA5 | ||||
| Biochemical Class | Acid anhydride hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Adenosine triphosphate | Ligand Info | |||
| Canonical SMILES | C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N | ||||
| InChI | 1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | ZKHQWZAMYRWXGA-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 5957 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6ASY BiP-ATP2 | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [1] |
| PDB Sequence |
SEDVGTVVGI
33 DLGTTYSCVG43 VFKNGRVEII53 ANDQGNRITP63 SYVAFTPEGE73 RLIGDAAKNQ 83 LTSNPENTVF93 DAKRLIGRTW103 NDPSVQQDIK113 FLPFKVVEKK123 TKPYIQVDIG 133 GGQTKTFAPE143 EISAMVLTKM153 KETAEAYLGK163 KVTHAVVTVP173 AYFNDAQRQA 183 TKDAGTIAGL193 NVMRIINEPT203 AAAIAYGLDK213 REGEKNILVF223 DLGGGTFDVS 233 LLTIDNGVFE243 VVATNGDTHL253 GGEDFDQRVM263 EHFIKLYKKK273 TGKDVRKDNR 283 AVQKLRREVE293 KAKRALSSQH303 QARIEIESFY313 EGEDFSETLT323 RAKFEELNMD 333 LFRSTMKPVQ343 KVLEDSDLKK353 SDIDEIVLVG363 GSTRIPKIQQ373 LVKEFFNGKE 383 PSRGINPDEA393 VAYGAAVQAG403 VLSGDQDTGD413 LVLLDVCPLT423 LGIETVGGVM 433 TKLIPRNTVV443 PTKKSQIFSV453 GGTVTIKVYE463 GERPLTKDNH473 LLGTFDLTGI 483 PPAPRGVPQI493 EVTFEIDVNG503 ILRVTAEDKG513 TGNKNKITIT523 NDQNRLTPEE 533 IERMVNDAEK543 FAEEDKKLKE553 RIDTRNELES563 YAYSLKNQIG573 DKEKLGGKLS 583 SEDKETMEKA593 VEEKIEWLES603 HQDADIEDFK613 AKKKELEEIV623 QPIISK |
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|
|
ASP34
3.915
LEU35
4.540
GLY36
3.326
THR37
2.660
THR38
3.028
TYR39
3.242
LYS96
2.736
GLU201
2.871
ASP224
4.765
GLY226
3.366
GLY227
2.734
GLY228
3.040
THR229
2.803
GLY255
3.388
|
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| PDB ID: 5E84 ATP-bound state of BiP | ||||||
| Method | X-ray diffraction | Resolution | 2.99 Å | Mutation | No | [2] |
| PDB Sequence |
SEDVGTVVGI
33 DLGTTYSCVG43 VFKNGRVEII53 ANDQGNRITP63 SYVAFTPEGE73 RLIGDAAKNQ 83 LTSNPENTVF93 DAKRLIGRTW103 NDPSVQQDIK113 FLPFKVVEKK123 TKPYIQVDIG 133 GGQTKTFAPE143 EISAMVLTKM153 KETAEAYLGK163 KVTHAVVTVP173 AYFNDAQRQA 183 TKDAGTIAGL193 NVMRIINEPT203 AAAIAYGLDK213 REGEKNILVF223 DLGGGAFDVS 233 LLTIDNGVFE243 VVATNGDTHL253 GGEDFDQRVM263 EHFIKLYKKK273 TGKDVRKDNR 283 AVQKLRREVE293 KAKRALSSQH303 QARIEIESFY313 EGEDFSETLT323 RAKFEELNMD 333 LFRSTMKPVQ343 KVLEDSDLKK353 SDIDEIVLVG363 GSTRIPKIQQ373 LVKEFFNGKE 383 PSRGINPDEA393 VAYGAAVQAG403 VLSGDQDTGD413 LVLLDVCPLT423 LGIETVGGVM 433 TKLIPRNTVV443 PTKKSQIFSV453 GGTVTIKVYE463 GERPLTKDNH473 LLGTFDLTGI 483 PPAPRGVPQI493 EVTFEIDVNG503 ILRVTAEDKG513 TGNKNKITIT523 NDQNRLTPEE 533 IERMVNDAEK543 FAEEDKKLKE553 RIDTRNELES563 YAYSLKNQIG573 DKEKLGGKLS 583 SEDKETMEKA593 VEEKIEWLES603 HQDADIEDFK613 AKKKELEEIV623 QPIISK |
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|
|
ASP34
3.714
LEU35
4.927
GLY36
3.281
THR37
2.785
THR38
2.773
TYR39
2.859
LYS96
2.370
GLU201
2.984
ASP224
4.625
LEU225
4.876
GLY226
3.378
GLY227
2.785
GLY228
3.180
ALA229
3.415
|
|||||
| PDB ID: 5F1X Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with ATP | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
DVGTVVGIDL
35 GTTYSCVGVF45 KNGRVEIIAN55 DQGNRITPSY65 VAFTPEGERL75 IGDAAKNQSN 87 PENTVFDAKR97 LIGRTWNDPS107 VQQDIKFLPF117 KVVEKKTKPY127 IQVDIGGGQT 137 KTFAPEEISA147 MVLTKMKETA157 EAYLGKKVTH167 AVVTVPAYFN177 DAQRQATKDA 187 GTIAGLNVMR197 IINEPTAAAI207 AYGLDKREGE217 KNILVFDLGG227 GTFDVSLLTI 237 DNGVFEVVAT247 NGDTHLGGED257 FDQRVMEHFI267 KLYKKKTGKD277 VRKDNRAVQK 287 LRREVEKAKR297 ALSSQHQARI307 EIESFYEGED317 FSETLTRAKF327 EELNMDLFRS 337 TMKPVQKVLE347 DSDLKKSDID357 EIVLVGGSTR367 IPKIQQLVKE377 FFNGKEPSRG 387 INPDEAVAYG397 AAVQAGVLSG407
|
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|
|
ASP34
3.953
GLY36
3.472
THR37
2.831
THR38
2.803
TYR39
2.782
ILE61
4.485
LYS96
4.642
ASP224
4.956
LEU225
4.594
GLY226
3.440
GLY227
3.186
GLY228
2.828
THR229
2.409
PHE230
4.871
|
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| PDB ID: 3LDL Crystal structure of human GRP78 (70kDa heat shock protein 5 / BIP) ATPase domain in complex with ATP | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [4] |
| PDB Sequence |
DVGTVVGIDL
35 GTTYSCVGVF45 KNGRVEIIAN55 DQGNRITPSY65 VAFTPEGERL75 IGDAAKNQLT 85 SNPENTVFDA95 KRLIGRTWND105 PSVQQDIKFL115 PFKVVEKKTK125 PYIQVDIGGG 135 QTKTFAPEEI145 SAMVLTKMKE155 TAEAYLGKKV165 THAVVTVPAY175 FNDAQRQATK 185 DAGTIAGLNV195 MRIINEPTAA205 AIAYGLDKRE215 GEKNILVFDL225 GGGTFDVSLL 235 TIDNGVFEVV245 ATNGDTHLGG255 EDFDQRVMEH265 FIKLYKKKTG275 KDVRKDNRAV 285 QKLRREVEKA295 KRALSSQHQA305 RIEIESFYEG315 EDFSETLTRA325 KFEELNMDLF 335 RSTMKPVQKV345 LEDSDLKKSD355 IDEIVLVGGS365 TRIPKIQQLV375 KEFFNGKEPS 385 RGINPDEAVA395 YGAAVQAGVL405 S
|
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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 .ATP or .ATP2 or .ATP3 or :3ATP;style chemicals stick;color identity;select .A:34 or .A:36 or .A:37 or .A:38 or .A:39 or .A:61 or .A:96 or .A:224 or .A:225 or .A:226 or .A:227 or .A:228 or .A:229 or .A:230 or .A:255 or .A:256 or .A:259 or .A:293 or .A:296 or .A:297 or .A:300 or .A:363 or .A:364 or .A:365 or .A:367 or .A:368 or .A:391; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP34
4.067
GLY36
3.433
THR37
2.539
THR38
2.698
TYR39
2.904
ILE61
4.710
LYS96
4.589
ASP224
4.967
LEU225
4.649
GLY226
3.370
GLY227
3.111
GLY228
2.705
THR229
2.499
PHE230
4.950
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. Nat Commun. 2017 Oct 31;8(1):1201. | ||||
| REF 2 | Close and Allosteric Opening of the Polypeptide-Binding Site in a Human Hsp70 Chaperone BiP. Structure. 2015 Dec 1;23(12):2191-2203. | ||||
| REF 3 | Probing the ATP Site of GRP78 with Nucleotide Triphosphate Analogs. PLoS One. 2016 May 4;11(5):e0154862. | ||||
| REF 4 | Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity. J Med Chem. 2011 Jun 23;54(12):4034-41. | ||||
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