Structure of PDB 1i5r Chain A Binding Site BS01

Receptor Information

>1i5r Chain A (length=285) Species: 9606 (Homo sapiens)

ARTVVLITGCSSGIGLHLAVRLASDPSQSFKVYATLRDLKTQGRLWEAAR
ALACPPGSLETLQLDVRDSKSVAAARERVTEGRVDVLVCNAGLGLLGPLE
ALGEDAVASVLDVNVVGTVRMLQAFLPDMKRRGSGRVLVTGSVGGLMGLP
FNDVYCASKFALEGLCESLAVLLLPFGVHLSLIECGPVHTAFMEKVLGSP
EEVLDRTDIHTFHRFYQYLAHSKQVFREAAQNPEEVAEVFLTALRAPKPT
LRYFTTERFLPLLRMRLDDPSGSNYVTAMHREVFG

Ligand information

• Ligand ID: HYC
• InChI: InChI=1S/C37H51N5O7/c1-37-15-14-25-24-13-11-23(43)16-21(24)10-12-26(25)27(37)17-22(33(37)47)8-6-4-2-3-5-7-9-29(44)48-18-28-31(45)32(46)36(49-28)42-20-41-30-34(38)39-19-40-35(30)42/h11,13,16,19-20,22,25-28,31-33,36,43,45-47H,2-10,12,14-15,17-18H2,1H3,(H2,38,39,40)/t22-,25+,26+,27-,28+,31+,32+,33-,36+,37-/m0/s1
• InChIKey: CKSDYJASHNGOOS-KTXOUVACSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: C[C@]12CC[C@@H]3c4ccc(cc4CC[C@H]3[C@@H]1C[C@@H]([C@@H]2O)CCCCCCCCC(=O)OC[C@@H]5[C@H]([C@H]([C@@H](O5)n6cnc7c6ncnc7N)O)O)O
  CACTVS 3.341: C[C@]12CC[C@H]3[C@@H](CCc4cc(O)ccc34)[C@@H]1C[C@H](CCCCCCCCC(=O)OC[C@H]5O[C@H]([C@H](O)[C@@H]5O)n6cnc7c(N)ncnc67)[C@@H]2O
  ACDLabs 10.04: O=C(OCC3OC(n2cnc1c(ncnc12)N)C(O)C3O)CCCCCCCCC6CC5C7CCc4cc(O)ccc4C7CCC5(C)C6O
  CACTVS 3.341: C[C]12CC[CH]3[CH](CCc4cc(O)ccc34)[CH]1C[CH](CCCCCCCCC(=O)OC[CH]5O[CH]([CH](O)[CH]5O)n6cnc7c(N)ncnc67)[CH]2O
  OpenEye OEToolkits 1.5.0: CC12CCC3c4ccc(cc4CCC3C1CC(C2O)CCCCCCCCC(=O)OCC5C(C(C(O5)n6cnc7c6ncnc7N)O)O)O
• Formula: C37 H51 N5 O7
• Name: O5'-[9-(3,17B-DIHYDROXY-1,3,5(10)-ESTRATRIEN-16B-YL)-NONANOYL]ADENOSINE;
  EM-1745
• ChEMBL: CHEMBL371948
• DrugBank: DB02323
• ZINC: ZINC000024617412
• PDB chain: 1i5r Chain A Residue 328

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1i5r A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity
• Resolution: 1.6 Å
• Binding residue (original residue number in PDB): G9 S11 S12 R37 L64 D65 V66 R67 A91 G92 L93 G94 S142 G144 M147 L149 Y155 G186 F192 M193 Y218 H221 V225 F259
• Binding residue (residue number reindexed from 1): G9 S11 S12 R37 L64 D65 V66 R67 A91 G92 L93 G94 S142 G144 M147 L149 Y155 G186 F192 M193 Y218 H221 V225 F259
• Annotation score: 1
• Binding affinity: MOAD: Ki=3nM
  PDBbind-CN: -logKd/Ki=8.52,Ki=3.0nM
  BindingDB: IC50=52nM,Ki=3nM

Enzymatic activity

• Enzyme Commision number: 1.1.1.51: 3(or 17)beta-hydroxysteroid dehydrogenase.
  1.1.1.62: 17beta-estradiol 17-dehydrogenase.

Gene Ontology

Molecular Function

• GO:0003824 catalytic activity
• GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
• GO:0005496 steroid binding
• GO:0005515 protein binding
• GO:0016491 oxidoreductase activity
• GO:0030283 testosterone dehydrogenase [NAD(P)+] activity
• GO:0036094 small molecule binding
• GO:0042803 protein homodimerization activity
• GO:0047035 testosterone dehydrogenase (NAD+) activity
• GO:0047045 testosterone 17-beta-dehydrogenase (NADP+) activity
• GO:0050661 NADP binding
• GO:0070401 NADP+ binding
• GO:0072582 17-beta-hydroxysteroid dehydrogenase (NADP+) activity
• GO:1903924 estradiol binding

Biological Process

• GO:0006629 lipid metabolic process
• GO:0006694 steroid biosynthetic process
• GO:0006703 estrogen biosynthetic process
• GO:0007040 lysosome organization
• GO:0007519 skeletal muscle tissue development
• GO:0008210 estrogen metabolic process
• GO:0010467 gene expression
• GO:0060348 bone development
• GO:0060612 adipose tissue development
• GO:0061370 testosterone biosynthetic process
• GO:0071248 cellular response to metal ion

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol

External links

• PDB: RCSB:1i5r, PDBe:1i5r, PDBj:1i5r
• PDBsum: 1i5r
• PubMed: 12223444
• UniProt: P14061|DHB1_HUMAN 17-beta-hydroxysteroid dehydrogenase type 1 (Gene Name=HSD17B1)