Structure of PDB 4zz3 Chain A Binding Site BS01

Receptor Information

>4zz3 Chain A (length=200) Species: 9606 (Homo sapiens)

ARVAVLISGTGSNLQALIDSTREPNSSAQIDIVISNKAAVAGLDKAERAG
IPTRVINHKLYKNRVEFDSAIDLVLEEFSIDIVCLAGFMRILSGPFVQKW
NGKMLNIHPSLLPSFKGSNAHEQALETGVTVTGCTVHFVAEDVDAGQIIL
QEAVPVKRGDTVATLSERVKLAEHKIFPAALQLVASGTVQLGENGKICWV

Ligand information

• Ligand ID: 4DW
• InChI: InChI=1S/C20H19N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,7-9,13H,3,6H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/b8-7+/t13-/m0/s1
• InChIKey: OOPGILDDKAKTLT-GWJCSSMESA-N
• SMILES:
  CACTVS 3.385: NC1=NC(=O)c2c(CCc3ccc(cc3)C(=O)N[C@@H](/C=C/C(O)=O)C(O)=O)c[nH]c2N1
  OpenEye OEToolkits 1.9.2: c1cc(ccc1CCc2c[nH]c3c2C(=O)N=C(N3)N)C(=O)NC(C=CC(=O)O)C(=O)O
  CACTVS 3.385: NC1=NC(=O)c2c(CCc3ccc(cc3)C(=O)N[CH](C=CC(O)=O)C(O)=O)c[nH]c2N1
  ACDLabs 12.01: c1(ccc(cc1)C(=O)NC(C(O)=O)[C@H]=[C@H]C(=O)O)CCc2c3c(nc2)NC(=NC3=O)N
  OpenEye OEToolkits 1.9.2: c1cc(ccc1CCc2c[nH]c3c2C(=O)N=C(N3)N)C(=O)N[C@@H](/C=C/C(=O)O)C(=O)O
• Formula: C20 H19 N5 O6
• Name: N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid;
  pemetrexed
• ZINC: ZINC000263620851
• PDB chain: 4zz3 Chain A Residue 1101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4zz3 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor alpha and the Proton-Coupled Folate Transporter in Human Tumors.
• Resolution: 2.504 Å
• Binding residue (original residue number in PDB): L892 F895 M896 R897 I898 L899 N913 V946 A947 E948 V950
• Binding residue (residue number reindexed from 1): L85 F88 M89 R90 I91 L92 N106 V139 A140 E141 V143
• Annotation score: 1
• Binding affinity: MOAD: Ki=1000nM
  PDBbind-CN: -logKd/Ki=6.00,Ki=1000nM

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:4zz3, PDBe:4zz3, PDBj:4zz3
• PDBsum: 4zz3
• PubMed: 26317331
• UniProt: P22102|PUR2_HUMAN Trifunctional purine biosynthetic protein adenosine-3 (Gene Name=GART)