Structure of PDB 5j9f Chain A Binding Site BS02

Receptor Information

>5j9f Chain A (length=200) Species: 9606 (Homo sapiens)

ARVAVLISGTGSNLQALIDSTREPNSSAQIDIVISNKAAVAGLDKAERAG
IPTRVINHKLYKNRVEFDSAIDLVLEEFSIDIVCLAGFMRILSGPFVAKW
NGKMLNIHPSLLPSFKGSNAHEQALETGVTVTGCTVHFVAEDVDAGQIIL
QEAVPVKRGDTVATLSERVKLAEHKIFPAALQLVASGTVQLGENGKICWV

Ligand information

• Ligand ID: 83A
• InChI: InChI=1S/C20H22N6O6/c21-20-25-16-13(18(30)26-20)9-12(23-16)7-8-22-11-3-1-10(2-4-11)17(29)24-14(19(31)32)5-6-15(27)28/h1-4,9,14,22H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,21,23,25,26,30)/t14-/m0/s1
• InChIKey: UFNWIIALSMNORN-AWEZNQCLSA-N
• SMILES:
  CACTVS 3.385: NC1=Nc2[nH]c(CCNc3ccc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O)cc2C(=O)N1
  CACTVS 3.385: NC1=Nc2[nH]c(CCNc3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)cc2C(=O)N1
  OpenEye OEToolkits 2.0.4: c1cc(ccc1C(=O)NC(CCC(=O)O)C(=O)O)NCCc2cc3c([nH]2)N=C(NC3=O)N
  ACDLabs 12.01: c31c(N=C(NC1=O)N)nc(CCNc2ccc(C(=O)NC(C(=O)O)CCC(O)=O)cc2)c3
  OpenEye OEToolkits 2.0.4: c1cc(ccc1C(=O)N[C@@H](CCC(=O)O)C(=O)O)NCCc2cc3c([nH]2)N=C(NC3=O)N
• Formula: C20 H22 N6 O6
• Name: N-(4-{[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)ethyl]amino}benzene-1-carbonyl)-L-glutamic acid;
  antifolate AGF183
• ChEMBL: CHEMBL4437824
• ZINC: ZINC000205771765
• PDB chain: 5j9f Chain A Residue 1102

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5j9f Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor alpha and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.
• Resolution: 2.1 Å
• Binding residue (original residue number in PDB): F895 M896 R897 I898 L899 V946 A947 V950 D951
• Binding residue (residue number reindexed from 1): F88 M89 R90 I91 L92 V139 A140 V143 D144
• Annotation score: 2
• Binding affinity: MOAD: Ki=59nM
  PDBbind-CN: -logKd/Ki=7.23,Ki=59nM
  BindingDB: IC50=666nM,Ki=59nM

Enzymatic activity

• Catalytic site (original residue number in PDB): N913 H915 T942 D951
• Catalytic site (residue number reindexed from 1): N106 H108 T135 D144
• Enzyme Commision number: 2.1.2.2: phosphoribosylglycinamide formyltransferase 1.
  6.3.3.1: phosphoribosylformylglycinamidine cyclo-ligase.
  6.3.4.13: phosphoribosylamine--glycine ligase.

Gene Ontology

Molecular Function

• GO:0004644 phosphoribosylglycinamide formyltransferase activity

Biological Process

• GO:0006189 'de novo' IMP biosynthetic process
• GO:0009058 biosynthetic process

External links

• PDB: RCSB:5j9f, PDBe:5j9f, PDBj:5j9f
• PDBsum: 5j9f
• PubMed: 27458733
• UniProt: P22102|PUR2_HUMAN Trifunctional purine biosynthetic protein adenosine-3 (Gene Name=GART)