Structure of PDB 3nu0 Chain A Binding Site BS02

Receptor Information
>3nu0 Chain A (length=186) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLV
IMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLT
EQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPE
IDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND
Ligand information
Ligand ID3TU
InChIInChI=1S/C24H21N5O6S/c25-24-27-20(32)19-18-11(2-1-3-16(18)36-21(19)28-24)9-26-13-4-5-14-12(8-13)10-29(22(14)33)15(23(34)35)6-7-17(30)31/h1-5,8,15,26H,6-7,9-10H2,(H,30,31)(H,34,35)(H3,25,27,28,32)/t15-/m0/s1
InChIKeyQPDXRVRRCIFNSL-HNNXBMFYSA-N
SMILES
SoftwareSMILES
CACTVS 3.370NC1=Nc2sc3cccc(CNc4ccc5c(CN([CH](CCC(O)=O)C(O)=O)C5=O)c4)c3c2C(=O)N1
CACTVS 3.370NC1=Nc2sc3cccc(CNc4ccc5c(CN([C@@H](CCC(O)=O)C(O)=O)C5=O)c4)c3c2C(=O)N1
OpenEye OEToolkits 1.7.0c1cc(c2c(c1)sc3c2C(=O)NC(=N3)N)CNc4ccc5c(c4)CN(C5=O)[C@@H](CCC(=O)O)C(=O)O
ACDLabs 12.01O=C(O)C(N5C(=O)c1c(cc(cc1)NCc4c2c(sc3N=C(NC(=O)c23)N)ccc4)C5)CCC(=O)O
OpenEye OEToolkits 1.7.0c1cc(c2c(c1)sc3c2C(=O)NC(=N3)N)CNc4ccc5c(c4)CN(C5=O)C(CCC(=O)O)C(=O)O
FormulaC24 H21 N5 O6 S
Name(2S)-2-(5-{[(2-amino-4-oxo-3,4-dihydro[1]benzothieno[2,3-d]pyrimidin-5-yl)methyl]amino}-1-oxo-1,3-dihydro-2H-isoindol-2-yl)pentanedioic acid
ChEMBLCHEMBL1738740
DrugBank
ZINCZINC000066165938
PDB chain3nu0 Chain A Residue 188 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB3nu0 Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors.
Resolution1.35 Å
Binding residue
(original residue number in PDB)		I7 V8 A9 E30 F31 F34 Q35 T56 P61 N64 R70 V115
Binding residue
(residue number reindexed from 1)		I7 V8 A9 E30 F31 F34 Q35 T56 P61 N64 R70 V115
Annotation score1
Binding affinityMOAD: ic50=0.1uM
BindingDB: IC50=100nM
Enzymatic activity
Catalytic site (original residue number in PDB) L22 E30
Catalytic site (residue number reindexed from 1) L22 E30
Enzyme Commision number 1.5.1.3: dihydrofolate reductase.
Gene Ontology
Molecular Function
GO:0000900 mRNA regulatory element binding translation repressor activity
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0004146 dihydrofolate reductase activity
GO:0005542 folic acid binding
GO:0016491 oxidoreductase activity
GO:0050661 NADP binding
GO:0070402 NADPH binding
GO:1990825 sequence-specific mRNA binding
Biological Process
GO:0006729 tetrahydrobiopterin biosynthetic process
GO:0006730 one-carbon metabolic process
GO:0017148 negative regulation of translation
GO:0031103 axon regeneration
GO:0031427 response to methotrexate
GO:0046452 dihydrofolate metabolic process
GO:0046653 tetrahydrofolate metabolic process
GO:0046654 tetrahydrofolate biosynthetic process
GO:0046655 folic acid metabolic process
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:2000121 regulation of removal of superoxide radicals
Cellular Component
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:3nu0, PDBe:3nu0, PDBj:3nu0
PDBsum3nu0
PubMed21550809
UniProtP00374|DYR_HUMAN Dihydrofolate reductase (Gene Name=DHFR)

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