Structure of PDB 4kak Chain B Binding Site BS02

Receptor Information
>4kak Chain B (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 ID06U
InChIInChI=1S/C22H23N5O/c1-4-20-19(21(23)27-22(24)26-20)6-5-14(2)16-11-17(13-18(12-16)28-3)15-7-9-25-10-8-15/h7-14H,4H2,1-3H3,(H4,23,24,26,27)/t14-/m0/s1
InChIKeyKEPLBUUTAQCZOE-AWEZNQCLSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CCc1nc(N)nc(N)c1C#C[CH](C)c2cc(OC)cc(c2)c3ccncc3
OpenEye OEToolkits 1.7.2CCc1c(c(nc(n1)N)N)C#C[C@H](C)c2cc(cc(c2)OC)c3ccncc3
CACTVS 3.370CCc1nc(N)nc(N)c1C#C[C@H](C)c2cc(OC)cc(c2)c3ccncc3
OpenEye OEToolkits 1.7.2CCc1c(c(nc(n1)N)N)C#CC(C)c2cc(cc(c2)OC)c3ccncc3
ACDLabs 12.01n3c(c(C#CC(c2cc(c1ccncc1)cc(OC)c2)C)c(nc3N)N)CC
FormulaC22 H23 N5 O
Name6-ethyl-5-{(3R)-3-[3-methoxy-5-(pyridin-4-yl)phenyl]but-1-yn-1-yl}pyrimidine-2,4-diamine
ChEMBLCHEMBL4483572
DrugBank
ZINCZINC000095589199
PDB chain4kak Chain B 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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PDB4kak Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		I7 V8 E30 F31 F34 S59 P61 N64
Binding residue
(residue number reindexed from 1)		I7 V8 E30 F31 F34 S59 P61 N64
Annotation score1
Binding affinityMOAD: ic50=1300nM
BindingDB: IC50=1300nM
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:4kak, PDBe:4kak, PDBj:4kak
PDBsum4kak
PubMed24053334
UniProtP00374|DYR_HUMAN Dihydrofolate reductase (Gene Name=DHFR)

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