Structure of PDB 3um8 Chain A Binding Site BS01

Receptor Information
>3um8 Chain A (length=547) Species: 5833 (Plasmodium falciparum) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
MMEQVCDVFDIYAICACCKVESKNEGKKNEVFNNYTFRGLGNKGVLPWKC
NSLDMKYFCAVTTYVNESKYEKLKYKRCKYLNKETKKLQNVVVMGRTSWE
SIPKKFKPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYK
CFIIGGSVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISV
SDVYTSNNTTLDFIIYKKTNNDDEEEDDFVYFNFNKEKEEKNKNSIHPND
FQIYNSLKYKYHPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFD
LSQYFPLLTTKKLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTRE
FLDNRKLFHREVNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIIN
LIKNDPTSRRILLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRS
CDLGLGVPFNIASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLK
IQLNRIPYPFPTLKLNPDIKNIEDFTISDFTIQNYVHHEKISMDMAA
Ligand information
Ligand ID1CY
InChIInChI=1S/C11H14ClN5/c1-11(2)16-9(13)15-10(14)17(11)8-5-3-7(12)4-6-8/h3-6H,1-2H3,(H4,13,14,15,16)
InChIKeyQMNFFXRFOJIOKZ-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.0CC1(N=C(N=C(N1c2ccc(cc2)Cl)N)N)C
CACTVS 3.352CC1(C)N=C(N)N=C(N)N1c2ccc(Cl)cc2
ACDLabs 11.02Clc1ccc(cc1)N2C(=NC(=NC2(C)C)N)N
FormulaC11 H14 Cl N5
Name1-(4-chlorophenyl)-6,6-dimethyl-1,6-dihydro-1,3,5-triazine-2,4-diamine;
Cycloguanil
ChEMBLCHEMBL747
DrugBankDB14763
ZINCZINC000000001233
PDB chain3um8 Chain A Residue 609 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB3um8 Combined Spatial Limitation around Residues 16 and 108 of Plasmodium falciparum Dihydrofolate Reductase Explains Resistance to Cycloguanil.
Resolution2.6 Å
Binding residue
(original residue number in PDB)		I14 C15 A16 D54 F58 S108 I112 I164
Binding residue
(residue number reindexed from 1)		I14 C15 A16 D54 F58 S98 I102 I154
Annotation score1
Binding affinityBindingDB: Ki=1.5nM
Enzymatic activity
Catalytic site (original residue number in PDB) L46 D54 E382 W404 Y430 C490 R510 D513
Catalytic site (residue number reindexed from 1) L46 D54 E321 W343 Y369 C429 R449 D452
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
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Biological Process
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Cellular Component
External links
PDB RCSB:3um8, PDBe:3um8, PDBj:3um8
PDBsum3um8
PubMed22526319
UniProtA7UD81

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