Structure of PDB 1pwm Chain A Binding Site BS02

Receptor Information

>1pwm Chain A (length=316) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

MASRILLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQ
NENEVGVAIQEKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDL
KLDYLDLYLIHWPTGFKPGKEFFPLDESGNVVPSDTNILDTWAAMEELVD
EGLVKAIGISNFNHLQVEMILNKPGLKYKPAVNQIECHPYLTQEKLIQYC
QSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAKHNKTTAQVLI
RFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF

Ligand information

Ligand ID

FID

InChI

InChI=1S/C12H10FN3O4/c13-5-1-2-7-6(3-5)12(4-8(20-7)9(14)17)10(18)15-11(19)16-12/h1-3,8H,4H2,(H2,14,17)(H2,15,16,18,19)/t8-,12-/m0/s1

InChIKey

WAAPEIZFCHNLKK-UFBFGSQYSA-N

SMILES

Software	SMILES
ACDLabs 10.04	Fc3ccc2OC(C(=O)N)CC1(C(=O)NC(=O)N1)c2c3
OpenEye OEToolkits 1.5.0	c1cc2c(cc1F)[C@@]3(C[C@H](O2)C(=O)N)C(=O)NC(=O)N3
OpenEye OEToolkits 1.5.0	c1cc2c(cc1F)C3(CC(O2)C(=O)N)C(=O)NC(=O)N3
CACTVS 3.341	NC(=O)[CH]1C[C]2(NC(=O)NC2=O)c3cc(F)ccc3O1
CACTVS 3.341	NC(=O)[C@@H]1C[C@]2(NC(=O)NC2=O)c3cc(F)ccc3O1

Formula

C12 H10 F N3 O4

Name

(2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4'-IMIDAZOLIDINE]-2',5'-DIONE;
FIDARESTAT

PDB chain

1pwm Chain A Residue 1320 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

Global view

Local view

Structure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]

PDB	1pwm 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	0.92 Å
Binding residue (original residue number in PDB)	W20 Y48 H110 W111 C298 L300
Binding residue (residue number reindexed from 1)	W21 Y49 H111 W112 C299 L301
Annotation score	1
Binding affinity	BindingDB: IC50=35nM,Kd=16nM

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

View graph for
Molecular Function

View graph for
Biological Process

View graph for
Cellular Component

External links

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

[Back to BioLiP]