Structure of PDB 1sej Chain D Binding Site BS04

Receptor Information
>1sej Chain D (length=519) Species: 237895 (Cryptosporidium hominis) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EKNVSIVVAASVLSSGIGINGQLPWSISEDLKFFSKITNNKCDSNKKNAL
IMGRKTWDSIGRRPLKNRIIVVISSSLPQDEADPNVVVFRNLEDSIENLM
NDDSIENIFVCGGESIYRDALKDNFVDRIYLTRVALEDIEFDTYFPEIPE
TFLPVYMSQTFCTKNISYDFMIFEKQEKKTLQNCDPARGQLKSIDDTVDL
LGEIFGIRKMGNRHKFPKEEIYNTPSIRFGREHYEFQYLDLLSRVLENGA
YRENRTGISTYSIFGQMMRFDMRESFPLLTTKKVAIRSIFEELIWFIKGD
TNGNHLIEKKVYIWSGNGSKEYLERIGLGHREENDLGPIYGFQWRHYNGE
YKTMHDDYTGVGVDQLAKLIETLKNNPKDRRHILTAWNPSALSQMALPPC
HVLSQYYVTNDNCLSCNLYQRSCDLGLGSPFNIASYAILTMMLAQVCGYE
PGELAIFIGDAHIYENHLTQLKEQLSRTPRPFPQLKFKRKVENIEDFKWE
DIELIGYYPYPTIKMDMAV
Ligand information
Ligand IDF89
InChIInChI=1S/C27H24N4O6/c1-14-29-21-7-4-16-3-2-15(10-20(16)24(21)25(34)30-14)12-28-18-5-6-19-17(11-18)13-31(26(19)35)22(27(36)37)8-9-23(32)33/h2-7,10-11,22,28H,8-9,12-13H2,1H3,(H,32,33)(H,36,37)(H,29,30,34)/t22-/m0/s1
InChIKeyBRVFNEZMTRVUGW-QFIPXVFZSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0CC1=Nc2ccc3ccc(cc3c2C(=O)N1)CNc4ccc5c(c4)CN(C5=O)[C@@H](CCC(=O)O)C(=O)O
CACTVS 3.341CC1=Nc2ccc3ccc(CNc4ccc5c(CN([C@@H](CCC(O)=O)C(O)=O)C5=O)c4)cc3c2C(=O)N1
OpenEye OEToolkits 1.5.0CC1=Nc2ccc3ccc(cc3c2C(=O)N1)CNc4ccc5c(c4)CN(C5=O)C(CCC(=O)O)C(=O)O
CACTVS 3.341CC1=Nc2ccc3ccc(CNc4ccc5c(CN([CH](CCC(O)=O)C(O)=O)C5=O)c4)cc3c2C(=O)N1
ACDLabs 10.04O=C(O)C(N5C(=O)c1c(cc(cc1)NCc4cc3c(ccc2N=C(NC(=O)c23)C)cc4)C5)CCC(=O)O
FormulaC27 H24 N4 O6
NameS)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC ACID;
FOLATE ANALOG 1843U89
ChEMBLCHEMBL169896
DrugBank
ZINCZINC000003871820
PDB chain1sej Chain D Residue 617 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB1sej Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance.
Resolution2.87 Å
Binding residue
(original residue number in PDB)		V9 V10 A11 L25 D32 L33 F36 S37 I62 L67 R70 T134
Binding residue
(residue number reindexed from 1)		V7 V8 A9 L23 D30 L31 F34 S35 I60 L65 R68 T132
Annotation score1
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 E292 W314 Y340 C400 R421 D424
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:1sej, PDBe:1sej, PDBj:1sej
PDBsum1sej
PubMed16511011
UniProtQ27552

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