Structure of PDB 7ctw Chain A Binding Site BS01

Receptor Information
>7ctw Chain A (length=534) Species: 5833 (Plasmodium falciparum) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EQVCDVFDIYAICACCKVEVFNNYTFRGLGNKGVLPWKCNSLDMKYFCAV
TTYVNESKYEKLKYKRCKYLNKETKKLQNVVVMGRTSWESIPKKFKPLSN
RINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFIIGGSVVYQ
EFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVYTSNNTTL
DFIIYKKTNNDDEEEDDFVYFNFNKEKEEKNKNSIHPNDFQIYNSLKYKY
HPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTTK
KLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHRE
VNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRRI
LLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFNI
ASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPFP
TLKLNPDIKNIEDFTISDFTIQNYVHHEKISMDM
Ligand information
Ligand IDNDP
InChIInChI=1S/C21H30N7O17P3/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(44-46(33,34)35)14(30)11(43-21)6-41-48(38,39)45-47(36,37)40-5-10-13(29)15(31)20(42-10)27-3-1-2-9(4-27)18(23)32/h1,3-4,7-8,10-11,13-16,20-21,29-31H,2,5-6H2,(H2,23,32)(H,36,37)(H,38,39)(H2,22,24,25)(H2,33,34,35)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
InChIKeyACFIXJIJDZMPPO-NNYOXOHSSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]4[C@H]([C@H]([C@@H](O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N
CACTVS 3.341NC(=O)C1=CN(C=CC1)[CH]2O[CH](CO[P](O)(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O[P](O)(O)=O)[CH]3O)n4cnc5c(N)ncnc45)[CH](O)[CH]2O
CACTVS 3.341NC(=O)C1=CN(C=CC1)[C@@H]2O[C@H](CO[P@@](O)(=O)O[P@](O)(=O)OC[C@H]3O[C@H]([C@H](O[P](O)(O)=O)[C@@H]3O)n4cnc5c(N)ncnc45)[C@@H](O)[C@H]2O
OpenEye OEToolkits 1.5.0c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OCC4C(C(C(O4)N5C=CCC(=C5)C(=O)N)O)O)O)OP(=O)(O)O)N
FormulaC21 H30 N7 O17 P3
NameNADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
ChEMBLCHEMBL407009
DrugBankDB02338
ZINCZINC000008215411
PDB chain7ctw Chain A Residue 701 [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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PDB7ctw Discovery of new non-pyrimidine scaffolds as Plasmodium falciparum DHFR inhibitors by fragment-based screening.
Resolution2.51 Å
Binding residue
(original residue number in PDB)		C15 A16 L40 G44 V45 L46 G105 R106 T107 S108 L127 S128 R129 T130 N144 I164 G166 S167 V168 V169 E172 V195
Binding residue
(residue number reindexed from 1)		C13 A14 L29 G33 V34 L35 G84 R85 T86 S87 L106 S107 R108 T109 N123 I143 G145 S146 V147 V148 E151 V174
Annotation score4
Enzymatic activity
Catalytic site (original residue number in PDB) L46 D54 E382 W404 Y430 C490 R510 D513
Catalytic site (residue number reindexed from 1) L35 D43 E310 W332 Y358 C418 R438 D441
Enzyme Commision number 1.5.1.3: dihydrofolate reductase.
2.1.1.45: thymidylate synthase.
Gene Ontology
Molecular Function
GO:0004146 dihydrofolate reductase activity
GO:0004799 thymidylate synthase activity
GO:0008168 methyltransferase activity
GO:0016491 oxidoreductase activity
GO:0016741 transferase activity, transferring one-carbon groups
Biological Process
GO:0006231 dTMP biosynthetic process
GO:0006730 one-carbon metabolic process
GO:0009165 nucleotide biosynthetic process
GO:0032259 methylation
GO:0046654 tetrahydrofolate biosynthetic process
Cellular Component
GO:0005739 mitochondrion
GO:0005829 cytosol

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:7ctw, PDBe:7ctw, PDBj:7ctw
PDBsum7ctw
PubMed33530764
UniProtP13922|DRTS_PLAFK Bifunctional dihydrofolate reductase-thymidylate synthase

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