Structure of PDB 5fct Chain B Binding Site BS03

Receptor Information

>5fct Chain B (length=287) Species: 10090 (Mus musculus)

RHGELQYLRQVEHILRCGFKKEDRTGTGTLSVFGMQARYSLRDEFPLLTT
KRVFWKGVLEELLWFIKGSTNAKELSSKGVRIWDANGSRDFLDSLGFSAR
QEGDLGPVYGFQWRHFGAEYKDMDSDYSGQGVDQLQKVIDTIKTNPDDRR
IIMCAWNPKDLPLMALPPCHALCQFYVVNGELSCQLYQRSGDMGLGVPFN
IASYALLTYMIAHITGLQPGDFVHTLGDAHIYLNHIEPLKIQLQREPRPF
PKLKILRKVETIDDFKVEDFQIEGYNPHPTIKMEMAV

Ligand information

• Ligand ID: C2F
• InChI: InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12-,13-/m0/s1
• InChIKey: ZNOVTXRBGFNYRX-STQMWFEESA-N
• SMILES:
  CACTVS 3.341: CN1[CH](CNc2ccc(cc2)C(=O)N[CH](CCC(O)=O)C(O)=O)CNC3=C1C(=O)NC(=N3)N
  ACDLabs 10.04: O=C(O)C(NC(=O)c1ccc(cc1)NCC2N(C=3C(=O)NC(=NC=3NC2)N)C)CCC(=O)O
  OpenEye OEToolkits 1.5.0: CN1C(CNC2=C1C(=O)NC(=N2)N)CNc3ccc(cc3)C(=O)NC(CCC(=O)O)C(=O)O
  OpenEye OEToolkits 1.5.0: C[N@@]1[C@H](CNC2=C1C(=O)NC(=N2)N)CNc3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
  CACTVS 3.341: CN1[C@@H](CNc2ccc(cc2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC3=C1C(=O)NC(=N3)N
• Formula: C20 H25 N7 O6
• Name: 5-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID
• ChEMBL: CHEMBL1231574
• DrugBank: DB11256
• ZINC: ZINC000002005305
• PDB chain: 5fct Chain B Residue 402

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5fct Mouse thymidylate synthase does not show the inactive conformation, observed for the human enzyme
• Resolution: 1.55 Å
• Binding residue (original residue number in PDB): V73 F74 I102 W103 N106 L186 D212 L215 G216 F219 M305 A306
• Binding residue (residue number reindexed from 1): V53 F54 I82 W83 N86 L166 D192 L195 G196 F199 M285 A286
• Annotation score: 2

Enzymatic activity

• Catalytic site (original residue number in PDB): E81 W103 Y129 C189 R209 D212
• Catalytic site (residue number reindexed from 1): E61 W83 Y109 C169 R189 D192
• 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:0097421 liver regeneration

Cellular Component

• GO:0005634 nucleus
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix

External links

• PDB: RCSB:5fct, PDBe:5fct, PDBj:5fct
• PDBsum: 5fct
• UniProt: P07607|TYSY_MOUSE Thymidylate synthase (Gene Name=Tyms)