Structure of PDB 6pfb Chain A Binding Site BS04

Receptor Information
>6pfb Chain A (length=505) Species: 237895 (Cryptosporidium hominis) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EKNVSIVVAASVLSSGIGINGQLPWSISEDLKFFSKITNNKCDSNKKNAL
IMGRKTWDSIGRRPLKNRIIVVISSSLPQDEADPNVVVFRNLEDSIENLM
NDDSIENIFVCGGESIYRDALKDNFVDRIYLTRVALEDIEFDTYFPEIPE
TFLPVYMSQTFCTKNISYDFMIFEKQLKSIDDTVDLLGEIFGIRKMGNRH
KFPKEEIYNTPSIRFGREHYEFQYLDLLSRVLENGAYRENRTGISTYSIF
GQMMRFDMRESFPLLTTKKVAIRSIFEELIWFIKGDTNGNHLIEKKVYIW
SGNGSKEYLERIGLGHREENDLGPIYGFQWRHYNGEYKTMHDDYTGVGVD
QLAKLIETLKNNPKDRRHILTAWNPSALSQMALPPCHVLSQYYVTNDNCL
SCNLYQRSCDLGLGSPFNIASYAILTMMLAQVCGYEPGELAIFIGDAHIY
ENHLTQLKEQLSRTPRPFPQLKFKRKVENIEDFKWEDIELIGYYPYPTIK
MDMAV
Ligand information
Ligand IDMTX
InChIInChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKeyFBOZXECLQNJBKD-ZDUSSCGKSA-N
SMILES
SoftwareSMILES
CACTVS 3.341CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O
CACTVS 3.341CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
OpenEye OEToolkits 1.5.0CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)NC(CCC(=O)O)C(=O)O
ACDLabs 10.04O=C(O)C(NC(=O)c1ccc(cc1)N(C)Cc2nc3c(nc2)nc(nc3N)N)CCC(=O)O
OpenEye OEToolkits 1.5.0CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
FormulaC20 H22 N8 O5
NameMETHOTREXATE
ChEMBLCHEMBL34259
DrugBankDB00563
ZINCZINC000001529323
PDB chain6pfb Chain A Residue 604 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB6pfb Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.
Resolution3.089 Å
Binding residue
(original residue number in PDB)		V9 V10 A11 L25 D32 F36 S37 R70 T134
Binding residue
(residue number reindexed from 1)		V7 V8 A9 L23 D30 F34 S35 R68 T132
Annotation score2
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 E278 W300 Y326 C386 R407 D410
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:6pfb, PDBe:6pfb, PDBj:6pfb
PDBsum6pfb
PubMed31536894
UniProtA0A0S4TER9

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