Structure of PDB 3cl9 Chain A Binding Site BS01

Receptor Information
>3cl9 Chain A (length=505) Species: 5693 (Trypanosoma cruzi) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SLFKIRMPETVAEGTRLALRAFSLVVAVDERGGIGDGRSIPWNVPEDMKF
FRDVTTKLRGKNVKPSPAKRNAVVMGRKTWDSIPPKFRPLPGRLNVVLSS
TLTTQHLLDNLHADSIVAVNGGLEQALQLLASPNYTPSIETVYCIGGGSV
YAEALRPPCVHLLQAIYRTTIRASESSCSVFFRVPESGTEAAAGIEWQRE
TISEELTSANGNETKYYFEKLIPRNREEEQYLSLVDRIIREGNVKHDRTG
VGTLSIFGAQMRFSLRNNRLPLLTTKRVFWRGVCEELLWFLRGETYAKKL
SDKGVHIWDDNGSRAFLDSRGLTEYEEMDLGPVYGFQWRHFGAAYTHHDA
NYDGQGVDQIKAIVETLKTNPDDRRMLFTAWNPSALPRMALPPCHLLAQF
YVSNGELSCMLYQRSCDMGLGVPFNIASYALLTILIAKATGLRPGELVHT
LGDAHVYSNHVEPCNEQLKRVPRAFPYLVFRREREFLEDYEEGDMEVIDY
APYPP
Ligand information
Ligand IDNAP
InChIInChI=1S/C21H28N7O17P3/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/h1-4,7-8,10-11,13-16,20-21,29-31H,5-6H2,(H7-,22,23,24,25,32,33,34,35,36,37,38,39)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
InChIKeyXJLXINKUBYWONI-NNYOXOHSSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0c1cc(c[n+](c1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N
CACTVS 3.341NC(=O)c1ccc[n+](c1)[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)c1ccc[n+](c1)[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 1.5.0c1cc(c[n+](c1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO[P@@](=O)([O-])O[P@](=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)n4cnc5c4ncnc5N)OP(=O)(O)O)O)O)O)C(=O)N
FormulaC21 H28 N7 O17 P3
NameNADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE;
2'-MONOPHOSPHOADENOSINE 5'-DIPHOSPHORIBOSE
ChEMBLCHEMBL295069
DrugBankDB03461
ZINC
PDB chain3cl9 Chain A Residue 601 [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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PDB3cl9 Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function.
Resolution3.3 Å
Binding residue
(original residue number in PDB)		A28 I35 S40 I41 G77 R78 K79 T80 L99 S100 S101 T102 N129 G130 G131 I154 G155 G156 G157 S158 Y160
Binding residue
(residue number reindexed from 1)		A27 I34 S39 I40 G76 R77 K78 T79 L98 S99 S100 T101 N120 G121 G122 I145 G146 G147 G148 S149 Y151
Annotation score4
Enzymatic activity
Catalytic site (original residue number in PDB) I41 D48 E295 W317 Y343 C403 R423 D426
Catalytic site (residue number reindexed from 1) I40 D47 E286 W308 Y334 C394 R414 D417
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:3cl9, PDBe:3cl9, PDBj:3cl9
PDBsum3cl9
PubMed18536013
UniProtQ27793|DRTS_TRYCR Bifunctional dihydrofolate reductase-thymidylate synthase

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