Structure of PDB 6lh9 Chain B Binding Site BS02

Receptor Information
>6lh9 Chain B (length=526) Species: 5833 (Plasmodium falciparum) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
QVCDVFDIYAICACCKVENEVFNNYTFRGLGNKGVLPWKCISLDMKYFRA
VTTYVNESKYEKLKYKRCKYLQNVVVMGRTNWESIPKKFKPLSNRINVIL
SRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFILGGSVVYQEFLEKK
LIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVYTSNNTTLDFIIYK
KTNDDEEEDDFVYFNFNKEKEEKNKNSIHPNDFQIYNSLKYKYHPEYQYL
NIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTTKKLFLRGI
IEELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHREVNDLGPI
YGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRRILLCAWNV
KDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFNIASYSIFT
HMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPFPTLKLNPD
IKNIEDFTISDFTIQNYVHHEKISMD
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 chain6lh9 Chain B Residue 902 [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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PDB6lh9 Flexible diaminodihydrotriazine inhibitors of Plasmodium falciparum dihydrofolate reductase: Binding strengths, modes of binding and their antimalarial activities.
Resolution2.644 Å
Binding residue
(original residue number in PDB)		C15 A16 L40 G44 V45 G105 R106 T107 N108 L127 S128 R129 T130 G166 S167 V168 V169 Y170 E172
Binding residue
(residue number reindexed from 1)		C12 A13 L30 G34 V35 G78 R79 T80 N81 L100 S101 R102 T103 G139 S140 V141 V142 Y143 E145
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) L36 D44 E303 W325 Y351 C411 R431 D434
Enzyme Commision number 1.5.1.3: dihydrofolate reductase.
2.1.1.45: thymidylate synthase.
Gene Ontology
Molecular Function
GO:0000166 nucleotide binding
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

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Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:6lh9, PDBe:6lh9, PDBj:6lh9
PDBsum6lh9
PubMed32294614
UniProtD9N170

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