Structure of PDB 4kn0 Chain A Binding Site BS01

Receptor Information

>4kn0 Chain A (length=205) Species: 9606 (Homo sapiens)

RTDLLNVCMDAKHHKTKPGPEDKLHDQCSPWKKNACCTASTSQELHKDTS
RLYNFNWDHCGKMEPACKRHFIQDTCLYECSPNLGPWIQQVNQSWRKERF
LDVPLCKEDCQRWWEDCHTSHTCKSNWHRGWDWTSGVNKCPAGALCRTFE
SYFPTPAALCEGLWSHSYKVSNYSRGSGRCIQMWFDSAQGNPNEEVARFY
AAAMH

Ligand information

• Ligand ID: MTX
• InChI: InChI=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
• InChIKey: FBOZXECLQNJBKD-ZDUSSCGKSA-N
• SMILES:
  CACTVS 3.341: CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O
  CACTVS 3.341: CN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
  OpenEye OEToolkits 1.5.0: CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)NC(CCC(=O)O)C(=O)O
  ACDLabs 10.04: O=C(O)C(NC(=O)c1ccc(cc1)N(C)Cc2nc3c(nc2)nc(nc3N)N)CCC(=O)O
  OpenEye OEToolkits 1.5.0: CN(Cc1cnc2c(n1)c(nc(n2)N)N)c3ccc(cc3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
• Formula: C20 H22 N8 O5
• Name: METHOTREXATE
• ChEMBL: CHEMBL34259
• DrugBank: DB00563
• ZINC: ZINC000001529323
• PDB chain: 4kn0 Chain A Residue 301

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4kn0 Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition.
• Resolution: 2.1 Å
• Binding residue (original residue number in PDB): Y76 F78 Y101 Q116 W118 H151 R152 G153 W154 W156 W187 S190
• Binding residue (residue number reindexed from 1): Y53 F55 Y78 Q93 W95 H128 R129 G130 W131 W133 W164 S167
• Annotation score: 1
• Binding affinity: MOAD: Kd=40nM
  PDBbind-CN: -logKd/Ki=7.40,Kd=40nM
  BindingDB: IC50=106nM

External links

• PDB: RCSB:4kn0, PDBe:4kn0, PDBj:4kn0
• PDBsum: 4kn0
• PubMed: 23934049
• UniProt: P14207|FOLR2_HUMAN Folate receptor beta (Gene Name=FOLR2)