Structure of PDB 3inv Chain A Binding Site BS02

Receptor Information
>3inv Chain A (length=514) Species: 5693 (Trypanosoma cruzi) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SLFKIRMPETVAEGTRLALRAFSLVVAVDEHGGIGDGRSIPWNVPEDMKF
FRDLTTKLRGKNVKPSPAKRNAVVMGRKTWDSIPPKFRPLPGRLNVVLSS
TLTTQHLLDGLPDEEKRNLHADSIVAVNGGLEQALRLLASPNYTPSIETV
YCIGGGSVYAEALRPPCVHLLQAIYRTTIRASESSCSVFFRVPESGTEAA
AGIEWQRETISEELTSANGNETKYYFEKLIPRNREEEQYLSLVDRIIREG
NVKHDRTGVGTLSIFGAQMRFSLRNNRLPLLTTKRVFWRGVCEELLWFLR
GETYAKKLSDKGVHIWDDNGSRAFLDSRGLTEYEEMDLGPVYGFQWRHFG
AAYTHHDANYDGQGVDQIKAIVETLKTNPDDRRMLFTAWNPSALPRMALP
PCHLLAQFYVSNGELSCMLYQRSCDMGLGVPFNIASYALLTILIAKATGL
RPGELVHTLGDAHVYSNHVEPCNEQLKRVPRAFPYLVFRREREFLEDYEE
GDMEVIDYAPYPPI
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 chain3inv Chain A Residue 602 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB3inv Structural basis of antifolate inhibition of Trypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase
Resolution2.37 Å
Binding residue
(original residue number in PDB)		V27 A28 I35 G38 R39 S40 I41 G77 R78 K79 T80 L99 S100 S101 G130 G131 I154 G155 G156 G157 S158 Y160
Binding residue
(residue number reindexed from 1)		V26 A27 I34 G37 R38 S39 I40 G76 R77 K78 T79 L98 S99 S100 G129 G130 I153 G154 G155 G156 S157 Y159
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 E294 W316 Y342 C402 R422 D425
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:3inv, PDBe:3inv, PDBj:3inv
PDBsum3inv
PubMed
UniProtQ27793|DRTS_TRYCR Bifunctional dihydrofolate reductase-thymidylate synthase

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