Structure of PDB 1u70 Chain A Binding Site BS01

Receptor Information
>1u70 Chain A (length=186) Species: 10090 (Mus musculus) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VRPLNCIVAVSQNMGIGKNGDRPWPPLRNEFKYFQRMTTTSSVEGKQNLV
IMGRKTWFSIPEKNRPLKDRINIVLSRELKEPPRGAHFLAKSLDDALRLI
EQPELASKVDMVWIVGGSSVYQEAMNQPGHLRLFVTRIMQEFESDTFFPE
IDLGKYKLLPEYPGVLSEVQEEKGIKYKFEVYEKKD
Ligand information
Ligand IDMTX
InChIInChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKeyFBOZXECLQNJBKD-ZDUSSCGKSA-N
SMILES
SoftwareSMILES
CACTVS 3.341CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O
CACTVS 3.341CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
OpenEye OEToolkits 1.5.0CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)NC(CCC(=O)O)C(=O)O
ACDLabs 10.04O=C(O)C(NC(=O)c1ccc(cc1)N(C)Cc2nc3c(nc2)nc(nc3N)N)CCC(=O)O
OpenEye OEToolkits 1.5.0CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
FormulaC20 H22 N8 O5
NameMETHOTREXATE
ChEMBLCHEMBL34259
DrugBankDB00563
ZINCZINC000001529323
PDB chain1u70 Chain A Residue 187 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB1u70 Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		I7 V8 R22 E30 F31 F34 Q35 I60 N64 K68 R70 V115
Binding residue
(residue number reindexed from 1)		I7 V8 R22 E30 F31 F34 Q35 I60 N64 K68 R70 V115
Annotation score2
Binding affinityMOAD: Ki=230nM
BindingDB: IC50=25nM,Ki=0.006000nM
Enzymatic activity
Catalytic site (original residue number in PDB) R22 E30
Catalytic site (residue number reindexed from 1) R22 E30
Enzyme Commision number 1.5.1.3: dihydrofolate reductase.
Gene Ontology
Molecular Function
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0004146 dihydrofolate reductase activity
GO:0016491 oxidoreductase activity
GO:0050661 NADP binding
GO:0051871 dihydrofolic acid binding
Biological Process
GO:0006729 tetrahydrobiopterin biosynthetic process
GO:0006730 one-carbon metabolic process
GO:0031103 axon regeneration
GO:0031427 response to methotrexate
GO:0035094 response to nicotine
GO:0035999 tetrahydrofolate interconversion
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:0005634 nucleus
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:1u70, PDBe:1u70, PDBj:1u70
PDBsum1u70
PubMed15681865
UniProtP00375|DYR_MOUSE Dihydrofolate reductase (Gene Name=Dhfr)

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