Structure of PDB 4l1w Chain A Binding Site BS02

Receptor Information

>4l1w Chain A (length=325) Species: 9606 (Homo sapiens)

SVDDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEAVKLAIEAGFHH
IDSAHVYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSNSHRPELVRPA
LERSLKNLQLDYVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATW
EAMEKCKDAGLAKSIGVSNFNHRLLEMILNKPGLKYKPVCNQVECHPYFN
QRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKH
KRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDG
LNRNVRYLTLDIFAGPPNYPFSDEY

Ligand information

• Ligand ID: STR
• InChI: InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
• InChIKey: RJKFOVLPORLFTN-LEKSSAKUSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC(=O)C1CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C
  ACDLabs 10.04: O=C4C=C2C(C1CCC3(C(C(=O)C)CCC3C1CC2)C)(C)CC4
  CACTVS 3.341: CC(=O)[CH]1CC[CH]2[CH]3CCC4=CC(=O)CC[C]4(C)[CH]3CC[C]12C
  CACTVS 3.341: CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
  OpenEye OEToolkits 1.5.0: CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C
• Formula: C21 H30 O2
• Name: PROGESTERONE
• ChEMBL: CHEMBL103
• DrugBank: DB00396
• ZINC: ZINC000004428529
• PDB chain: 4l1w Chain A Residue 402

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4l1w Human 3-alpha hydroxysteroid dehydrogenase type 3 (3 alpha-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20 alpha-HSD activity
• Resolution: 2.2 Å
• Binding residue (original residue number in PDB): Y24 V128 I129 W227 L308
• Binding residue (residue number reindexed from 1): Y26 V130 I131 W229 L310
• Annotation score: 5

Enzymatic activity

• Catalytic site (original residue number in PDB): D50 Y55 K84 H117
• Catalytic site (residue number reindexed from 1): D52 Y57 K86 H119
• Enzyme Commision number: 1.-.-.-
  1.1.1.112: indanol dehydrogenase.
  1.1.1.209: 3(or 17)alpha-hydroxysteroid dehydrogenase.
  1.1.1.357: 3alpha-hydroxysteroid 3-dehydrogenase.
  1.1.1.53: 3alpha(or 20beta)-hydroxysteroid dehydrogenase.
  1.1.1.62: 17beta-estradiol 17-dehydrogenase.
  1.3.1.20: trans-1,2-dihydrobenzene-1,2-diol dehydrogenase.

Gene Ontology

Molecular Function

• GO:0004032 aldose reductase (NADPH) activity
• GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
• GO:0016491 oxidoreductase activity
• GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
• GO:0031406 carboxylic acid binding
• GO:0032052 bile acid binding
• GO:0047023 androsterone dehydrogenase activity
• GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase activity
• GO:0047086 ketosteroid monooxygenase activity
• GO:0047115 trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
• GO:0047718 indanol dehydrogenase activity

Biological Process

• GO:0006693 prostaglandin metabolic process
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007586 digestion
• GO:0008202 steroid metabolic process
• GO:0008284 positive regulation of cell population proliferation
• GO:0030855 epithelial cell differentiation
• GO:0042448 progesterone metabolic process
• GO:0044597 daunorubicin metabolic process
• GO:0044598 doxorubicin metabolic process
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0071395 cellular response to jasmonic acid stimulus
• GO:0071799 cellular response to prostaglandin D stimulus

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol

External links

• PDB: RCSB:4l1w, PDBe:4l1w, PDBj:4l1w
• PDBsum: 4l1w
• PubMed: 24434280
• UniProt: P52895|AK1C2_HUMAN Aldo-keto reductase family 1 member C2 (Gene Name=AKR1C2)