Structure of PDB 3gug Chain A Binding Site BS01

Receptor Information

>3gug Chain A (length=318) Species: 9606 (Homo sapiens)

QCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLY
NNEEQVGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKN
LQLDYVDLYLIHFPVSVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCK
DAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNQRKLLDF
CKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPVLCALAKKHKRTPALI
ALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLNRNVRY
LTVDIFAGPPNYPFSDEY

Ligand information

• Ligand ID: NAP
• InChI: InChI=1S/C21H28N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
• InChIKey: XJLXINKUBYWONI-NNYOXOHSSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1cc(c[n+](c1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N
  CACTVS 3.341: NC(=O)c1ccc[n+](c1)[CH]2O[CH](CO[P]([O-])(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O[P](O)(O)=O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
  CACTVS 3.341: NC(=O)c1ccc[n+](c1)[C@@H]2O[C@H](CO[P]([O-])(=O)O[P@@](O)(=O)OC[C@H]3O[C@H]([C@H](O[P](O)(O)=O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
  OpenEye OEToolkits 1.5.0: c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N
• Formula: C21 H28 N7 O17 P3
• Name: NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE;
  2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE
• ChEMBL: CHEMBL295069
• DrugBank: DB03461
• PDB chain: 3gug Chain A Residue 350

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3gug Crystal structure of AKR1C1 L308V mutant in complex with NADP and 3,5-dichlorosalicylic acid
• Resolution: 1.9 Å
• Binding residue (original residue number in PDB): G22 T23 Y24 D50 Y55 H117 Q190 Y216 S217 L219 S221 H222 A253 L268 K270 S271 R276 Q279 N280
• Binding residue (residue number reindexed from 1): G17 T18 Y19 D45 Y50 H112 Q185 Y211 S212 L214 S216 H217 A248 L263 K265 S266 R271 Q274 N275
• Annotation score: 4

Enzymatic activity

• Catalytic site (original residue number in PDB): D50 Y55 K84 H117
• Catalytic site (residue number reindexed from 1): D45 Y50 K79 H112
• Enzyme Commision number: 1.1.1.-
  1.1.1.112: indanol dehydrogenase.
  1.1.1.149: 20alpha-hydroxysteroid dehydrogenase.
  1.1.1.209: 3(or 17)alpha-hydroxysteroid dehydrogenase.
  1.1.1.210: 3beta-(or 20alpha)-hydroxysteroid dehydrogenase.
  1.1.1.357: 3alpha-hydroxysteroid 3-dehydrogenase.
  1.1.1.51: 3(or 17)beta-hydroxysteroid 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:0004033 aldo-keto reductase (NADPH) activity
• GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
• GO:0005515 protein binding
• GO:0016491 oxidoreductase activity
• GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
• GO:0030283 testosterone dehydrogenase [NAD(P)+] activity
• GO:0031406 carboxylic acid binding
• GO:0032052 bile acid binding
• GO:0033703 3beta-hydroxy-5beta-steroid dehydrogenase activity
• GO:0033764 steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
• GO:0047006 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
• GO:0047023 androsterone dehydrogenase activity
• GO:0047024 5alpha-androstane-3beta,17beta-diol dehydrogenase activity
• GO:0047042 androsterone dehydrogenase (B-specific) activity
• GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase activity
• GO:0047045 testosterone 17-beta-dehydrogenase (NADP+) 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:0001523 retinoid metabolic process
• GO:0006629 lipid metabolic process
• GO:0006693 prostaglandin metabolic process
• GO:0006805 xenobiotic metabolic process
• GO:0007586 digestion
• GO:0008206 bile acid metabolic process
• GO:0015721 bile acid and bile salt transport
• GO:0030299 intestinal cholesterol absorption
• GO:0030855 epithelial cell differentiation
• GO:0042448 progesterone metabolic process
• GO:0042574 retinal metabolic process
• GO:0042632 cholesterol homeostasis
• GO:0044597 daunorubicin metabolic process
• GO:0044598 doxorubicin metabolic process
• GO:0046683 response to organophosphorus
• GO:0071395 cellular response to jasmonic acid stimulus
• GO:2000379 positive regulation of reactive oxygen species metabolic process

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:3gug, PDBe:3gug, PDBj:3gug
• PDBsum: 3gug
• UniProt: Q04828|AK1C1_HUMAN Aldo-keto reductase family 1 member C1 (Gene Name=AKR1C1)