Structure of PDB 6pfi Chain D Binding Site BS04

Receptor Information

>6pfi Chain D (length=507) Species: 237895 (Cryptosporidium hominis)

EKNVSIVVAASVLSSGIGINGQLPWSISEDLKFFSKITNNKCDSNKKNAL
IMGRKTWDSIGRRPLKNRIIVVISSSLPQDEADPNVVVFRNLEDSIENLM
NDDSIENIFVCGGESIYRDALKDNFVDRIYLTRVALEDIEFDTYFPEIPE
TFLPVYMSQTFCTKNISYDFMIFEKQEKLKSIDDTVDLLGEIFGIRKMGN
RHKFPKEEIYNTPSIRFGREHYEFQYLDLLSRVLENGAYRENRTGISTYS
IFGQMMRFDMRESFPLLTTKKVAIRSIFEELIWFIKGDTNGNHLIEKKVY
IWSGNGSKEYLERIGLGHREENDLGPIYGFQWRHYNGEYKTMHDDYTGVG
VDQLAKLIETLKNNPKDRRHILTAWNPSALSQMALPPCHVLSQYYVTNDN
CLSCNLYQRSCDLGLGSPFNIASYAILTMMLAQVCGYEPGELAIFIGDAH
IYENHLTQLKEQLSRTPRPFPQLKFKRKVENIEDFKWEDIELIGYYPYPT
IKMDMAV

Ligand information

• Ligand ID: OEP
• InChI: InChI=1S/C23H19N5O6/c24-23-27-19-18(21(32)28-23)15(10-25-19)7-11-1-3-12(4-2-11)20(31)26-16-8-14(22(33)34)6-5-13(16)9-17(29)30/h1-6,8,10H,7,9H2,(H,26,31)(H,29,30)(H,33,34)(H4,24,25,27,28,32)
• InChIKey: FDEJWGPULAIBRF-UHFFFAOYSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1cc(ccc1Cc2c[nH]c3c2C(=O)NC(=N3)N)C(=O)Nc4cc(ccc4CC(=O)O)C(=O)O
  ACDLabs 12.01: c14c(c(cn1)Cc2ccc(cc2)C(Nc3c(CC(O)=O)ccc(c3)C(O)=O)=O)C(=O)NC(=N4)N
  CACTVS 3.385: NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)Nc4cc(ccc4CC(O)=O)C(O)=O)c2C(=O)N1
• Formula: C23 H19 N5 O6
• Name: 3-({4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}amino)-4-(carboxymethyl)benzoic acid
• ChEMBL: CHEMBL4451239
• PDB chain: 6pfi Chain D Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6pfi Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
• Resolution: 2.89 Å
• Binding residue (original residue number in PDB): K284 S290 I315 N319 L429 G430 F433 M519
• Binding residue (residue number reindexed from 1): K270 S276 I301 N305 L415 G416 F419 M505
• 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 E280 W302 Y328 C388 R409 D412
• 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:6pfi, PDBe:6pfi, PDBj:6pfi
• PDBsum: 6pfi
• PubMed: 31536894
• UniProt: A0A0S4TER9