Structure of PDB 4keb Chain A Binding Site BS02

Receptor Information
>4keb 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 ID1QZ
InChIInChI=1S/C26H25N5O/c1-4-24-23(25(27)31-26(28)30-24)9-8-16(2)18-12-19(14-20(13-18)32-3)21-7-5-6-17-15-29-11-10-22(17)21/h5-7,10-16H,4H2,1-3H3,(H4,27,28,30,31)/t16-/m1/s1
InChIKeyMGLLCDAARSVGLO-MRXNPFEDSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CCc1c(c(nc(n1)N)N)C#C[C@@H](C)c2cc(cc(c2)OC)c3cccc4c3ccnc4
CACTVS 3.370CCc1nc(N)nc(N)c1C#C[C@@H](C)c2cc(OC)cc(c2)c3cccc4cnccc34
OpenEye OEToolkits 1.7.6CCc1c(c(nc(n1)N)N)C#CC(C)c2cc(cc(c2)OC)c3cccc4c3ccnc4
CACTVS 3.370CCc1nc(N)nc(N)c1C#C[CH](C)c2cc(OC)cc(c2)c3cccc4cnccc34
ACDLabs 12.01n4c(c(C#CC(c3cc(c2c1ccncc1ccc2)cc(OC)c3)C)c(nc4N)N)CC
FormulaC26 H25 N5 O
Name6-ethyl-5-{(3S)-3-[3-(isoquinolin-5-yl)-5-methoxyphenyl]but-1-yn-1-yl}pyrimidine-2,4-diamine
ChEMBL
DrugBank
ZINCZINC000095591779
PDB chain4keb Chain A Residue 202 [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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PDB4keb Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.
Resolution1.45 Å
Binding residue
(original residue number in PDB)		I7 V8 A9 L22 E30 F31 F34 P61 N64 L67
Binding residue
(residue number reindexed from 1)		I7 V8 A9 L22 E30 F31 F34 P61 N64 L67
Annotation score1
Binding affinityMOAD: ic50=45nM
BindingDB: IC50=45nM
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:4keb, PDBe:4keb, PDBj:4keb
PDBsum4keb
PubMed24053334
UniProtP00374|DYR_HUMAN Dihydrofolate reductase (Gene Name=DHFR)

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