Structure of PDB 3iro Chain B Binding Site BS02

Receptor Information
>3iro Chain B (length=515) Species: 5693 (Trypanosoma cruzi) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
LFKIRMPETVAEGTRLALRAFSLVVAVDEHGGIGDGRSIPWNVPEDMKFF
RDLTTKLRGKNVKPSPAKRNAVVMGRKTWDSIPPKFRPLPGRLNVVLSST
LTTQHLLDGLPDEEKRNLHADSIVAVNGGLEQALRLLASPNYTPSIETVY
CIGGGSVYAEALRPPCVHLLQAIYRTTIRASESSCSVFFRVPESGTEAAA
GIEWQRETISEELTSANGNETKYYFEKLIPRNREEEQYLSLVDRIIREGN
VKHDRTGVGTLSIFGAQMRFSLRNNRLPLLTTKRVFWRGVCEELLWFLRG
ETYAKKLSDKGVHIWDDNGSRAFLDSRGLTEYEEMDLGPVYGFQWRHFGA
AYTHHDANYDGQGVDQIKAIVETLKTNPDDRRMLFTAWNPSALPRMALPP
CHLLAQFYVSNGELSCMLYQRSCDMGLGVPFNIASYALLTILIAKATGLR
PGELVHTLGDAHVYSNHVEPCNEQLKRVPRAFPYLVFRREREFLEDYEEG
DMEVIDYAPYPPISM
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 chain3iro Chain B Residue 702 [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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PDB3iro Structural basis of antifolate inhibition of Trypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase
Resolution2.8 Å
Binding residue
(original residue number in PDB)		A28 G38 R39 I41 G77 R78 K79 T80 L99 S100 S101 G130 G131 G155 G156 G157 S158 Y160
Binding residue
(residue number reindexed from 1)		A26 G36 R37 I39 G75 R76 K77 T78 L97 S98 S99 G128 G129 G153 G154 G155 S156 Y158
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) I39 D46 E293 W315 Y341 C401 R421 D424
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

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:3iro, PDBe:3iro, PDBj:3iro
PDBsum3iro
PubMed
UniProtQ27793|DRTS_TRYCR Bifunctional dihydrofolate reductase-thymidylate synthase

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