Structure of PDB 6pfd Chain B Binding Site BS04

Receptor Information

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

EKNVSIVVAASVLSSGIGINGQLPWSISEDLKFFSKITNNKCDSNKKNAL
IMGRKTWDSIGRRPLKNRIIVVISSSLPQDEADPNVVVFRNLEDSIENLM
NDDSIENIFVCGGESIYRDALKDNFVDRIYLTRVALEDIEFDTYFPEIPE
TFLPVYMSQTFCTKNISYDFMIFEKQELKSIDDTVDLLGEIFGIRKMGNR
HKFPKEEIYNTPSIRFGREHYEFQYLDLLSRVLENGAYRENRTGISTYSI
FGQMMRFDMRESFPLLTTKKVAIRSIFEELIWFIKGDTNGNHLIEKKVYI
WSGNGSKEYLERIGLGHREENDLGPIYGFQWRHYNGEYKTMHDDYTGVGV
DQLAKLIETLKNNPKDRRHILTAWNPSALSQMALPPCHVLSQYYVTNDNC
LSCNLYQRSCDLGLGSPFNIASYAILTMMLAQVCGYEPGELAIFIGDAHI
YENHLTQLKEQLSRTPRPFPQLKFKRKVENIEDFKWEDIELIGYYPYPTI
KMDMAV

Ligand information

• Ligand ID: OEJ
• InChI: InChI=1S/C22H17N5O6/c23-22-26-17-16(19(29)27-22)13(9-24-17)7-10-1-3-11(4-2-10)18(28)25-15-8-12(20(30)31)5-6-14(15)21(32)33/h1-6,8-9H,7H2,(H,25,28)(H,30,31)(H,32,33)(H4,23,24,26,27,29)
• InChIKey: UKZJDHHDTGYQBX-UHFFFAOYSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1cc(ccc1Cc2c[nH]c3c2C(=O)NC(=N3)N)C(=O)Nc4cc(ccc4C(=O)O)C(=O)O
  CACTVS 3.385: NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)Nc4cc(ccc4C(O)=O)C(O)=O)c2C(=O)N1
  ACDLabs 12.01: C(c1ccc(cc1)Cc2cnc3c2C(=O)NC(=N3)N)(Nc4cc(C(O)=O)ccc4C(O)=O)=O
• Formula: C22 H17 N5 O6
• Name: 2-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)benzene-1,4-dicarboxylic acid
• ChEMBL: CHEMBL4562561
• PDB chain: 6pfd Chain B Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6pfd Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
• Resolution: 3.324 Å
• Binding residue (original residue number in PDB): K284 I315 L429 F433 I515
• Binding residue (residue number reindexed from 1): K269 I300 L414 F418 I500
• 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:6pfd, PDBe:6pfd, PDBj:6pfd
• PDBsum: 6pfd
• PubMed: 31536894
• UniProt: A0A0S4TER9