Structure of PDB 1pwl Chain A Binding Site BS01

Receptor Information

>1pwl Chain A (length=316) Species: 9606 (Homo sapiens)

MASRILLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQ
NENEVGVAIQEKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDL
KLDYLDLYLIHWPTGFKPGKEFFPLDESGNVVPSDTNILDTWAAMEELVD
EGLVKAIGISNFNHLQVEMILNKPGLKYKPAVNQIECHPYLTQEKLIQYC
QSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAKHNKTTAQVLI
RFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF

Ligand information

• Ligand ID: BFI
• InChI: InChI=1S/C19H11BrF2N2O4/c20-10-2-1-9(14(22)5-10)8-24-16(26)12-4-3-11(21)6-13(12)19(18(24)28)7-15(25)23-17(19)27/h1-6H,7-8H2,(H,23,25,27)/t19-/m1/s1
• InChIKey: BMHZAHGTGIZZCT-LJQANCHMSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1cc2c(cc1F)[C@@]3(CC(=O)NC3=O)C(=O)N(C2=O)Cc4ccc(cc4F)Br
  CACTVS 3.341: Fc1ccc2C(=O)N(Cc3ccc(Br)cc3F)C(=O)[C]4(CC(=O)NC4=O)c2c1
  ACDLabs 10.04: Brc1ccc(c(F)c1)CN4C(=O)c2ccc(F)cc2C3(C(=O)NC(=O)C3)C4=O
  CACTVS 3.341: Fc1ccc2C(=O)N(Cc3ccc(Br)cc3F)C(=O)[C@]4(CC(=O)NC4=O)c2c1
  OpenEye OEToolkits 1.5.0: c1cc2c(cc1F)C3(CC(=O)NC3=O)C(=O)N(C2=O)Cc4ccc(cc4F)Br
• Formula: C19 H11 Br F2 N2 O4
• Name: 2[4-BROMO-2-FLUOROPHENYL)METHYL]-6-FLUOROSPIRO[ISOQUINOLINE-4-(1H),3'-PYRROLIDINE]-1,2',3,5'(2H)-TETRONE;
  MINALRESTAT
• ChEMBL: CHEMBL292963
• DrugBank: DB07450
• ZINC: ZINC000000597385
• PDB chain: 1pwl Chain A Residue 320

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1pwl Ultrahigh resolution drug design. II. Atomic resolution structures of human aldose reductase holoenzyme complexed with Fidarestat and Minalrestat: implications for the binding of cyclic imide inhibitors
• Resolution: 1.1 Å
• Binding residue (original residue number in PDB): W20 Y48 W79 H110 W111 F122 W219 C298 A299 L300
• Binding residue (residue number reindexed from 1): W21 Y49 W80 H111 W112 F123 W220 C299 A300 L301
• Annotation score: 1
• Binding affinity: BindingDB: IC50=25nM,Kd=5.5nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D43 Y48 K77 H110
• Catalytic site (residue number reindexed from 1): D44 Y49 K78 H111
• Enzyme Commision number: 1.1.1.21: aldose reductase.
  1.1.1.300: NADP-retinol dehydrogenase.
  1.1.1.372: D/L-glyceraldehyde reductase.
  1.1.1.54: allyl-alcohol dehydrogenase.

Gene Ontology

Molecular Function

• GO:0001758 retinal dehydrogenase activity
• GO:0004032 aldose reductase (NADPH) activity
• GO:0005515 protein binding
• GO:0009055 electron transfer activity
• GO:0016491 oxidoreductase activity
• GO:0036130 prostaglandin H2 endoperoxidase reductase activity
• GO:0043795 glyceraldehyde oxidoreductase activity
• GO:0047655 allyl-alcohol dehydrogenase activity
• GO:0047939 L-glucuronate reductase activity
• GO:0047956 glycerol dehydrogenase (NADP+) activity
• GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity

Biological Process

• GO:0001523 retinoid metabolic process
• GO:0002070 epithelial cell maturation
• GO:0003091 renal water homeostasis
• GO:0005975 carbohydrate metabolic process
• GO:0006629 lipid metabolic process
• GO:0006693 prostaglandin metabolic process
• GO:0006700 C21-steroid hormone biosynthetic process
• GO:0019853 L-ascorbic acid biosynthetic process
• GO:0035809 regulation of urine volume
• GO:0042572 retinol metabolic process
• GO:0043066 negative regulation of apoptotic process
• GO:0044597 daunorubicin metabolic process
• GO:0044598 doxorubicin metabolic process
• GO:0046370 fructose biosynthetic process
• GO:0071475 cellular hyperosmotic salinity response
• GO:0072205 metanephric collecting duct development

Cellular Component

• GO:0005615 extracellular space
• GO:0005654 nucleoplasm
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005829 cytosol
• GO:0070062 extracellular exosome

External links

• PDB: RCSB:1pwl, PDBe:1pwl, PDBj:1pwl
• PDBsum: 1pwl
• PubMed: 15146479
• UniProt: P15121|ALDR_HUMAN Aldo-keto reductase family 1 member B1 (Gene Name=AKR1B1)