Structure of PDB 5noo Chain A Binding Site BS02

Receptor Information

>5noo Chain A (length=287) Species: 6239 (Caenorhabditis elegans)

QVHLNQDEYKYLKQVEQILREGTRRDDRTGTGTISIFGMQSKYCLRNGTI
PLLTTKRVYWKGVLEELLWFISGSTDGKLLMEKNVKIWEKNGDRAFLDNL
GFTSREEGDLGPVYGFQWRHFGAKYVDCHTDYSGQGVDQLAEVIRQIKEQ
PDSRRIIMSAWNPSDLGQMVLPPCHTMCQFYVDNGELSCQLYQRSGDMGL
GVPFNLASYGLLTHMIAKVCGLKPGTLVHTLGDAHVYSNHVDALKIQLDR
EPYAFPKIRFTRDVASIDDFTSDMIALDDYKCHPKIP

Ligand information

• Ligand ID: D16
• InChI: InChI=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
• InChIKey: IVTVGDXNLFLDRM-HNNXBMFYSA-N
• SMILES:
  ACDLabs 12.01: O=C(c3sc(N(C)Cc2ccc1NC(=NC(=O)c1c2)C)cc3)NC(C(=O)O)CCC(=O)O
  CACTVS 3.370: CN(Cc1ccc2NC(=NC(=O)c2c1)C)c3sc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O
  OpenEye OEToolkits 1.7.6: CC1=NC(=O)c2cc(ccc2N1)CN(C)c3ccc(s3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
  CACTVS 3.370: CN(Cc1ccc2NC(=NC(=O)c2c1)C)c3sc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
  OpenEye OEToolkits 1.7.6: CC1=NC(=O)c2cc(ccc2N1)CN(C)c3ccc(s3)C(=O)NC(CCC(=O)O)C(=O)O
• Formula: C21 H22 N4 O6 S
• Name: TOMUDEX;
  ZD1694;
  Raltitrexed
• ChEMBL: CHEMBL225071
• DrugBank: DB00293
• ZINC: ZINC000003832372
• PDB chain: 5noo Chain A Residue 402

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5noo Crystal structures of nematode (parasitic T. spiralis and free living C. elegans), compared to mammalian, thymidylate synthases (TS). Molecular docking and molecular dynamics simulations in search for nematode-specific inhibitors of TS.
• Resolution: 2.9 Å
• Binding residue (original residue number in PDB): Y82 I110 D220 L223 G224 F227 Y260
• Binding residue (residue number reindexed from 1): Y59 I87 D197 L200 G201 F204 Y237
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): E89 W111 Y137 C197 R217 D220
• Catalytic site (residue number reindexed from 1): E66 W88 Y114 C174 R194 D197
• Enzyme Commision number: 2.1.1.45: thymidylate synthase.

Gene Ontology

Molecular Function

• GO:0004799 thymidylate synthase activity
• GO:0008168 methyltransferase activity
• GO:0016741 transferase activity, transferring one-carbon groups

Biological Process

• GO:0006231 dTMP biosynthetic process
• GO:0006235 dTTP biosynthetic process
• GO:0009165 nucleotide biosynthetic process
• GO:0032259 methylation

External links

• PDB: RCSB:5noo, PDBe:5noo, PDBj:5noo
• PDBsum: 5noo
• PubMed: 28826032
• UniProt: Q9Y052