Structure of PDB 6pf9 Chain B Binding Site BS03

Receptor Information

>6pf9 Chain B (length=506) Species: 237895 (Cryptosporidium hominis)

EKNVSIVVAASVLSSGIGINGQLPWSISEDLKFFSKITNNKCDSNKKNAL
IMGRKTWDSIGRRPLKNRIIVVISSSLPQDEADPNVVVFRNLEDSIENLM
NDDSIENIFVCGGESIYRDALKDNFVDRIYLTRVALEDIEFDTYFPEIPE
TFLPVYMSQTFCTKNISYDFMIFEKQELKSIDDTVDLLGEIFGIRKMGNR
HKFPKEEIYNTPSIRFGREHYEFQYLDLLSRVLENGAYRENRTGISTYSI
FGQMMRFDMRESFPLLTTKKVAIRSIFEELIWFIKGDTNGNHLIEKKVYI
WSGNGSKEYLERIGLGHREENDLGPIYGFQWRHYNGEYKTMHDDYTGVGV
DQLAKLIETLKNNPKDRRHILTAWNPSALSQMALPPCHVLSQYYVTNDNC
LSCNLYQRSCDLGLGSPFNIASYAILTMMLAQVCGYEPGELAIFIGDAHI
YENHLTQLKEQLSRTPRPFPQLKFKRKVENIEDFKWEDIELIGYYPYPTI
KMDMAV

Ligand information

• Ligand ID: OF7
• InChI: InChI=1S/C22H19N5O4/c23-22-26-19-18(21(31)27-22)15(11-24-19)9-12-5-7-13(8-6-12)20(30)25-16-4-2-1-3-14(16)10-17(28)29/h1-8,11H,9-10H2,(H,25,30)(H,28,29)(H4,23,24,26,27,31)
• InChIKey: NCEMLZMBZDJVMM-UHFFFAOYSA-N
• SMILES:
  CACTVS 3.385: NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)Nc4ccccc4CC(O)=O)c2C(=O)N1
  OpenEye OEToolkits 2.0.7: c1ccc(c(c1)CC(=O)O)NC(=O)c2ccc(cc2)Cc3c[nH]c4c3C(=O)NC(=N4)N
  ACDLabs 12.01: N1=C(NC(=O)c2c1ncc2Cc3ccc(cc3)C(=O)Nc4ccccc4CC(=O)O)N
• Formula: C22 H19 N5 O4
• Name: [2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)phenyl]acetic acid
• ChEMBL: CHEMBL4447254
• PDB chain: 6pf9 Chain B Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6pf9 Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
• Resolution: 2.89 Å
• Binding residue (original residue number in PDB): S290 I315 L429 F433
• Binding residue (residue number reindexed from 1): S275 I300 L414 F418
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): L25 D32 E294 W316 Y342 C402 R423 D426
• Catalytic site (residue number reindexed from 1): L23 D30 E279 W301 Y327 C387 R408 D411
• Enzyme Commision number: 1.5.1.3: dihydrofolate reductase.
  2.1.1.45: thymidylate synthase.

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• 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

External links

• PDB: RCSB:6pf9, PDBe:6pf9, PDBj:6pf9
• PDBsum: 6pf9
• PubMed: 31536894
• UniProt: A0A0S4TER9