Structure of PDB 5x5q Chain B Binding Site BS02

Receptor Information
>5x5q Chain B (length=287) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFGMQARYSLRDEFPLLT
TKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDSLGFST
REEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDR
RIIMCAWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPF
NIASYALLTYMIAHITGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRP
FPKLRILRKVEKIDDFKAEDFQIEGYNPHPTIKMEMA
Ligand information
Ligand IDD16
InChIInChI=1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1
InChIKeyIVTVGDXNLFLDRM-HNNXBMFYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(c3sc(N(C)Cc2ccc1NC(=NC(=O)c1c2)C)cc3)NC(C(=O)O)CCC(=O)O
CACTVS 3.370CN(Cc1ccc2NC(=NC(=O)c2c1)C)c3sc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O
OpenEye OEToolkits 1.7.6CC1=NC(=O)c2cc(ccc2N1)CN(C)c3ccc(s3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
CACTVS 3.370CN(Cc1ccc2NC(=NC(=O)c2c1)C)c3sc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
OpenEye OEToolkits 1.7.6CC1=NC(=O)c2cc(ccc2N1)CN(C)c3ccc(s3)C(=O)NC(CCC(=O)O)C(=O)O
FormulaC21 H22 N4 O6 S
NameTOMUDEX;
ZD1694;
Raltitrexed
ChEMBLCHEMBL225071
DrugBankDB00293
ZINCZINC000003832372
PDB chain5x5q Chain B Residue 402 [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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PDB5x5q Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states
Resolution2.79 Å
Binding residue
(original residue number in PDB)		I108 D218 L221 G222 F225 Y258 M311
Binding residue
(residue number reindexed from 1)		I83 D193 L196 G197 F200 Y233 M286
Annotation score1
Binding affinityBindingDB: IC50=29000nM
Enzymatic activity
Catalytic site (original residue number in PDB) E87 W109 Y135 C195 R215 D218
Catalytic site (residue number reindexed from 1) E62 W84 Y110 C170 R190 D193
Enzyme Commision number 2.1.1.45: thymidylate synthase.
Gene Ontology
Molecular Function
GO:0000900 mRNA regulatory element binding translation repressor activity
GO:0003729 mRNA binding
GO:0004799 thymidylate synthase activity
GO:0005542 folic acid binding
GO:0008168 methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
GO:0042803 protein homodimerization activity
GO:1901363 heterocyclic compound binding
GO:1990825 sequence-specific mRNA binding
Biological Process
GO:0006206 pyrimidine nucleobase metabolic process
GO:0006231 dTMP biosynthetic process
GO:0006235 dTTP biosynthetic process
GO:0006417 regulation of translation
GO:0007623 circadian rhythm
GO:0009165 nucleotide biosynthetic process
GO:0009410 response to xenobiotic stimulus
GO:0009636 response to toxic substance
GO:0014070 response to organic cyclic compound
GO:0017148 negative regulation of translation
GO:0019860 uracil metabolic process
GO:0032259 methylation
GO:0032570 response to progesterone
GO:0033189 response to vitamin A
GO:0034097 response to cytokine
GO:0035999 tetrahydrofolate interconversion
GO:0045471 response to ethanol
GO:0046653 tetrahydrofolate metabolic process
GO:0046683 response to organophosphorus
GO:0048589 developmental growth
GO:0051216 cartilage development
GO:0051384 response to glucocorticoid
GO:0051593 response to folic acid
GO:0060574 intestinal epithelial cell maturation
GO:0071897 DNA biosynthetic process
GO:0097421 liver regeneration
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0005829 cytosol

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:5x5q, PDBe:5x5q, PDBj:5x5q
PDBsum5x5q
PubMed28634233
UniProtP04818|TYSY_HUMAN Thymidylate synthase (Gene Name=TYMS)

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