Structure of PDB 1z3n Chain A Binding Site BS02

Receptor Information

>1z3n 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

3NA

InChI

InChI=1S/C18H11F3N2O2S/c19-11-6-12(20)18-17(16(11)21)22-14(26-18)5-9-7-23(8-15(24)25)13-4-2-1-3-10(9)13/h1-4,6-7H,5,8H2,(H,24,25)

InChIKey

KYHVTMFADJNSGS-UHFFFAOYSA-N

SMILES

Software	SMILES
OpenEye OEToolkits 1.5.0	c1ccc2c(c1)c(cn2CC(=O)O)Cc3nc4c(c(cc(c4s3)F)F)F
ACDLabs 10.04	O=C(O)Cn2c1ccccc1c(c2)Cc3nc4c(F)c(F)cc(F)c4s3
CACTVS 3.341	OC(=O)Cn1cc(Cc2sc3c(F)cc(F)c(F)c3n2)c4ccccc14

Formula

C18 H11 F3 N2 O2 S

Name

{3-[(4,5,7-TRIFLUORO-1,3-BENZOTHIAZOL-2-YL)METHYL]-1H-INDOL-1-YL}ACETIC ACID;
3-[(4,5,7-TRIFLUOROBENZOTHIAZOL-2-YL)METHYL]INDOLE-N-ACETIC ACID

PDB chain

1z3n Chain A Residue 320 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	1z3n Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications
Resolution	1.04 Å
Binding residue (original residue number in PDB)	W20 Y48 H110 W111 F122 W219 A299 L300 C303 Y309
Binding residue (residue number reindexed from 1)	W21 Y49 H111 W112 F123 W220 A300 L301 C304 Y310
Annotation score	1
Binding affinity	MOAD: ic50=5nM BindingDB: IC50=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

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Molecular Function

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Biological Process

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Cellular Component

External links

PDB	RCSB:1z3n, PDBe:1z3n, PDBj:1z3n
PDBsum	1z3n
PubMed	15857120
UniProt	P15121\|ALDR_HUMAN Aldo-keto reductase family 1 member B1 (Gene Name=AKR1B1)

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