Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T62265 | Target Info | |||
| Target Name | Deoxyhypusine synthase (DHPS) | ||||
| Synonyms | DHS | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | DHPS | ||||
| Biochemical Class | Alkyl aryl transferase | ||||
| UniProt ID | |||||
| 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: 6XXJ Crystal Structure of Human Deoxyhypusine Synthase in complex with spermidine and NAD | ||||||
| Method | X-ray diffraction | Resolution | 1.41 Å | Mutation | No | [1] |
| PDB Sequence |
EAPAGALAAV
17 LKHSSTLPPE27 STQVRGYDFN37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN 67 AMIEKKLEPL77 SQDEDQHADL87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR 117 YLVQHNMVDV127 LVTTAGGVEE137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG 167 NLLVPNENYK178 FEDWLMPILD188 QMVMEQNTEG198 VKWTPSKMIA208 RLGKEINNPE 218 SVYYWAQKNH228 IPVFSPALTD238 GSLGDMIFFH248 SYKNPGLVLD258 IVEDLRLINT 268 QAIFAKCTGM278 IILGGGVVKH288 HIANANLMRN298 GADYAVYINT308 AQEFDGSDSG 318 ARPDEAVSWG328 KIRVDAQPVK338 VYADASLVFP348 LLVAETFAQK358 MDAFM |
|||||
|
|
THR104
3.382
SER105
3.465
ASN106
2.864
LEU107
3.710
SER109
3.098
THR131
2.515
ALA132
3.100
GLY133
3.072
GLU136
3.504
GLU137
3.022
ILE166
3.956
ALA235
4.973
ASP238
2.502
GLY239
4.062
LEU281
4.971
|
|||||
| PDB ID: 7A6T Crystal Structure of Asn173Ser variant of Human Deoxyhypusine Synthase in complex with NAD and spermidine | ||||||
| Method | X-ray diffraction | Resolution | 1.66 Å | Mutation | Yes | [2] |
| PDB Sequence |
STQVRGYDFN
37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN67 AMIEKKLEPL77 SQDEDQHADL 87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR117 YLVQHNMVDV127 LVTTAGGVEE 137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG167 NLLVPSENYK178 FEDWLMPILD 188 QMVMEQNTEG198 VKWTPSKMIA208 RLGKEINNPE218 SVYYWAQKNH228 IPVFSPALTD 238 GSLGDMIFFH248 SYKNPGLVLD258 IVEDLRLINT268 QAIFAKCTGM278 IILGGGVVKH 288 HIANANLMRN298 GADYAVYINT308 AQEFDGSDSG318 ARPDEAVSWG328 KIRVDAQPVK 338 VYADASLVFP348 LLVAETFAQK358 MDAFM
|
|||||
|
|
THR104
2.823
SER105
2.624
ASN106
2.039
LEU107
2.811
SER109
3.082
THR131
1.873
ALA132
2.100
GLY133
2.257
GLY134
4.538
GLU136
2.665
GLU137
2.292
ILE166
3.265
ALA235
4.449
ASP238
1.960
GLY239
2.698
|
|||||
| PDB ID: 6XXI Crystal Structure of Human Deoxyhypusine Synthase in complex with NAD | ||||||
| Method | X-ray diffraction | Resolution | 1.68 Å | Mutation | No | [1] |
| PDB Sequence |
STQVRGYDFN
37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN67 AMIEKKLEPL77 HADLTQSRRP 93 LTSCTIFLGY103 TSNLISSGIR113 ETIRYLVQHN123 MVDVLVTTAG133 GVEEDLIKCL 143 APTYLGEFSL153 RGKELRENGI163 NRIGNLLVPN173 ENYKFEDWLM184 PILDQMVMEQ 194 NTEGVKWTPS204 KMIARLGKEI214 NNPESVYYWA224 QKNHIPVFSP234 ALTDGSLGDM 244 IFFHSYKNPG254 LVLDIVEDLR264 LINTQAIFAK274 CTGMIILGGG284 VVKHHIANAN 294 LMRNGADYAV304 YINTAQEFDG314 SDSGARPDEA324 VSWGKIRVDA334 QPVKVYADAS 344 LVFPLLVAET354 FAQKMDAFM
|
|||||
|
|
THR104
2.724
SER105
2.044
ASN106
2.052
LEU107
2.788
SER109
3.198
THR131
1.764
ALA132
1.985
GLY133
1.884
GLY134
3.804
GLU136
2.599
GLU137
2.352
ILE166
3.054
TYR176
4.426
ALA235
3.632
ASP238
2.378
GLY239
2.513
|
|||||
| PDB ID: 1RLZ Deoxyhypusine synthase holoenzyme in its high ionic strength, low pH crystal form | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [3] |
| PDB Sequence |
APAGALAAVL
18 KHSSTLPPES28 TQVRGYDFNR38 GVNYRALLEA48 FGTTGFQATN58 FGRAVQQVNA 68 MIEKKLEPLT95 SCTIFLGYTS105 NLISSGIRET115 IRYLVQHNMV125 DVLVTTAGGV 135 EEDLIKCLAP145 TYLGEFSLRG155 KELRENGINR165 IGNLLVPNEN175 YCKFEDWLMP 185 ILDQMVMEQN195 TEGVKWTPSK205 MIARLGKEIN215 NPESVYYWAQ225 KNHIPVFSPA 235 LTDGSLGDMI245 FFHSYKNPGL255 VLDIVEDLRL265 INTQAIFAKC275 TGMIILGGGV 285 VKHHIANANL295 MRNGADYAVY305 INTAQEFDGS315 DSGARPDEAV325 SWGKIRVDAQ 335 PVKVYADASL345 VFPLLVAETF355 AQKMDAFMHE365 KNED
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAD or .NAD2 or .NAD3 or :3NAD;style chemicals stick;color identity;select .A:104 or .A:105 or .A:106 or .A:107 or .A:109 or .A:131 or .A:132 or .A:133 or .A:136 or .A:137 or .A:166 or .A:235 or .A:238 or .A:239 or .A:281 or .A:282 or .A:283 or .A:284 or .A:306 or .A:307 or .A:308 or .A:309 or .A:317 or .A:341 or .A:342 or .A:343 or .A:344; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR104
3.394
SER105
2.944
ASN106
2.723
LEU107
3.378
SER109
3.638
THR131
2.998
ALA132
3.464
GLY133
3.307
GLU136
3.927
GLU137
2.969
ILE166
3.915
ALA235
4.500
ASP238
2.439
GLY239
4.536
|
|||||
| PDB ID: 1ROZ Deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form | ||||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | No | [3] |
| PDB Sequence |
STQVRGYDFN
37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN67 AMIEKKLEPL77 SQDEDQHADL 87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR117 YLVQHNMVDV127 LVTTAGGVEE 137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG167 NLLVPNENYC177 KFEDWLMPIL 187 DQMVMEQNTE197 GVKWTPSKMI207 ARLGKEINNP217 ESVYYWAQKN227 HIPVFSPALT 237 DGSLGDMIFF247 HSYKNPGLVL257 DIVEDLRLIN267 TQAIFAKCTG277 MIILGGGVVK 287 HHIANANLMR297 NGADYAVYIN307 TAQEFDGSDS317 GARPDEAVSW327 GKIRVDAQPV 337 KVYADASLVF347 PLLVAETFAQ357 KMDAFM
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAD or .NAD2 or .NAD3 or :3NAD;style chemicals stick;color identity;select .A:104 or .A:105 or .A:106 or .A:107 or .A:109 or .A:131 or .A:132 or .A:133 or .A:136 or .A:137 or .A:166 or .A:235 or .A:238 or .A:239 or .A:281 or .A:282 or .A:283 or .A:284 or .A:285 or .A:306 or .A:307 or .A:308 or .A:309 or .A:317 or .A:341 or .A:342 or .A:343 or .A:344; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR104
3.301
SER105
2.866
ASN106
2.879
LEU107
3.462
SER109
3.675
THR131
2.618
ALA132
2.972
GLY133
3.328
GLU136
3.872
GLU137
4.905
ILE166
4.107
ALA235
4.694
ASP238
2.518
GLY239
4.084
|
|||||
| PDB ID: 1RQD deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form with the inhibitor GC7 bound in the active site | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [3] |
| PDB Sequence |
STQVRGYDFN
37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN67 AMIEKKLEPL77 SQDEDQHADL 87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR117 YLVQHNMVDV127 LVTTAGGVEE 137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG167 NLLVPNENYC177 KFEDWLMPIL 187 DQMVMEQNTE197 GVKWTPSKMI207 ARLGKEINNP217 ESVYYWAQKN227 HIPVFSPALT 237 DGSLGDMIFF247 HSYKNPGLVL257 DIVEDLRLIN267 TQAIFAKCTG277 MIILGGGVVK 287 HHIANANLMR297 NGADYAVYIN307 TAQEFDGSDS317 GARPDEAVSW327 GKIRVDAQPV 337 KVYADASLVF347 PLLVAETFAQ357 KMDAFMH
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAD or .NAD2 or .NAD3 or :3NAD;style chemicals stick;color identity;select .A:104 or .A:105 or .A:106 or .A:107 or .A:109 or .A:131 or .A:132 or .A:133 or .A:136 or .A:137 or .A:166 or .A:235 or .A:238 or .A:239 or .A:282 or .A:283 or .A:284 or .A:285 or .A:306 or .A:307 or .A:308 or .A:309 or .A:317 or .A:341 or .A:342 or .A:343 or .A:344; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR104
3.419
SER105
3.146
ASN106
2.893
LEU107
3.745
SER109
3.324
THR131
2.585
ALA132
3.052
GLY133
3.634
GLU136
3.741
GLU137
3.262
ILE166
4.092
ALA235
4.321
ASP238
2.308
GLY239
4.323
|
|||||
| PDB ID: 6P4V 1.65 Angstrom ternary complex of Deoxyhypusine synthase with cofactor NAD and spermidine mimic inhibitor GC7 | ||||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [4] |
| PDB Sequence |
STQVRGYDFN
37 RGVNYRALLE47 AFGTTGFQAT57 NFGRAVQQVN67 AMIEKKLEPL77 SQDEDQHADL 87 TQSRRPLTSC97 TIFLGYTSNL107 ISSGIRETIR117 YLVQHNMVDV127 LVTTAGGVEE 137 DLIKCLAPTY147 LGEFSLRGKE157 LRENGINRIG167 NLLVPNENYC177 KFEDWLMPIL 187 DQMVMEQNTE197 GVKWTPSKMI207 ARLGKEINNP217 ESVYYWAQKN227 HIPVFSPALT 237 DGSLGDMIFF247 HSYKNPGLVL257 DIVEDLRLIN267 TQAIFAKCTG277 MIILGGGVVK 287 HHIANANLMR297 NGADYAVYIN307 TAQEFDGSDS317 GARPDEAVSW327 GKIRVDAQPV 337 KVYADASLVF347 PLLVAETFAQ357 KMDAFM
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAD or .NAD2 or .NAD3 or :3NAD;style chemicals stick;color identity;select .A:104 or .A:105 or .A:106 or .A:107 or .A:109 or .A:131 or .A:132 or .A:133 or .A:136 or .A:137 or .A:166 or .A:235 or .A:238 or .A:239 or .A:240 or .A:282 or .A:283 or .A:284 or .A:285 or .A:306 or .A:307 or .A:308 or .A:309 or .A:317 or .A:341 or .A:342 or .A:343 or .A:344; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR104
3.291
SER105
2.815
ASN106
2.918
LEU107
3.579
SER109
2.905
THR131
2.567
ALA132
3.065
GLY133
3.130
GLU136
3.443
GLU137
2.831
ILE166
3.899
ALA235
4.949
ASP238
2.542
GLY239
3.939
|
|||||
| PDB ID: 1DHS CRYSTAL STRUCTURE OF THE NAD COMPLEX OF HUMAN DEOXYHYPUSINE SYNTHASE | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
APAGALAAVL
18 KHSSTLPPES28 TQVRGYDFNR38 GVNYRALLEA48 FGTTGFQATN58 FGRAVQQVNA 68 MIEKKLEPLT95 SCTIFLGYTS105 NLISSGIRET115 IRYLVQHNMV125 DVLVTTAGGV 135 EEDLIKCLAP145 TYLGEFSLRG155 KELRENGINR165 IGNLLVPNEN175 YCKFEDWLMP 185 ILDQMVMEQN195 TEGVKWTPSK205 MIARLGKEIN215 NPESVYYWAQ225 KNHIPVFSPA 235 LTDGSLGDMI245 FFHSYKNPGL255 VLDIVEDLRL265 INTQAIFAKC275 TGMIILGGGV 285 VKHHIANANL295 MRNGADYAVY305 INTAQEFDGS315 DSGARPDEAV325 SWGKIRVDAQ 335 PVKVYADASL345 VFPLLVAETF355 AQKMDAFMHE365 KNED
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .NAD or .NAD2 or .NAD3 or :3NAD;style chemicals stick;color identity;select .A:104 or .A:105 or .A:106 or .A:107 or .A:109 or .A:131 or .A:132 or .A:133 or .A:136 or .A:137 or .A:166 or .A:238 or .A:239 or .A:281 or .A:282 or .A:283 or .A:284 or .A:285 or .A:306 or .A:307 or .A:308 or .A:309 or .A:317 or .A:341 or .A:342 or .A:343 or .A:344; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR104
3.174
SER105
2.840
ASN106
2.954
LEU107
3.480
SER109
2.844
THR131
2.651
ALA132
3.323
GLY133
3.086
GLU136
3.752
GLU137
3.053
ILE166
3.697
ASP238
2.623
GLY239
4.449
LEU281
4.908
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase. Biomolecules. 2020 Mar 30;10(4):522. | ||||
| REF 2 | Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders. Nat Commun. 2023 Mar 27;14(1):1698. | ||||
| REF 3 | A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex. J Biol Chem. 2004 Jul 2;279(27):28697-705. | ||||
| REF 4 | Discovery of Novel Allosteric Inhibitors of Deoxyhypusine Synthase. J Med Chem. 2020 Mar 26;63(6):3215-3226. | ||||
| REF 5 | Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site. Structure. 1998 Jan 15;6(1):23-32. | ||||
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