Structure of PDB 5svr Chain A Binding Site BS01

Receptor Information

>5svr Chain A (length=327) Species: 9606 (Homo sapiens)

WTIGIINRVVQLLIISYFVGWVFLHEKAYQVRDTAIESSVVTKVKGSGLY
ANRVMDVSDYVTPPQGTSVFVIITKMIVTENQMQGFCPESEEKYRCVSDS
QCGPERLPGGGILTGRCVNYSSVLRTCEIQGWCPTEVDTVETPIMMEAEN
FTIFIKNSIRFPLFNFEKGNLLPNLTARDMKTCRFHPDKDPFCPILRVGD
VVKFAGQDFAKLARTGGVLGIKIGWVCDLDKAWDQCIPKYSFTRLDSVSE
KSSVSPGYNFRFAKYYKMENGSEYRTLLKAFGIRFDVLVYGNAGKFNIIP
TIISSVAAFTSVGVGTVLCDIILLNFL

Ligand information

• Ligand ID: 71C
• InChI: InChI=1S/C33H27NO8/c35-30(25-17-27(32(38)39)28(33(40)41)18-26(25)31(36)37)34(29-15-7-10-21-9-4-5-14-24(21)29)19-20-8-6-13-23(16-20)42-22-11-2-1-3-12-22/h1-6,8-9,11-14,16-18,29H,7,10,15,19H2,(H,36,37)(H,38,39)(H,40,41)/t29-/m0/s1
• InChIKey: VQGBOYBIENNKMI-LJAQVGFWSA-N
• SMILES:
  ACDLabs 12.01: c1(c(cc(C(O)=O)c(c1)C(=O)O)C(O)=O)C(=O)N(Cc2cccc(c2)Oc3ccccc3)C4CCCc5ccccc45
  CACTVS 3.385: OC(=O)c1cc(C(O)=O)c(cc1C(O)=O)C(=O)N(Cc2cccc(Oc3ccccc3)c2)[CH]4CCCc5ccccc45
  OpenEye OEToolkits 2.0.5: c1ccc(cc1)Oc2cccc(c2)CN(C3CCCc4c3cccc4)C(=O)c5cc(c(cc5C(=O)O)C(=O)O)C(=O)O
  CACTVS 3.385: OC(=O)c1cc(C(O)=O)c(cc1C(O)=O)C(=O)N(Cc2cccc(Oc3ccccc3)c2)[C@H]4CCCc5ccccc45
• Formula: C33 H27 N O8
• Name: 5-{[(3-phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl}benzene-1,2,4-tricarboxylic acid;
  antagonist A-317491
• ChEMBL: CHEMBL596234
• ZINC: ZINC000003990058
• PDB chain: 5svr Chain A Residue 405

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5svr X-ray structures define human P2X3 receptor gating cycle and antagonist action.
• Resolution: 3.13 Å
• Binding residue (original residue number in PDB): S273 V274 R281
• Binding residue (residue number reindexed from 1): S253 V254 R261
• Annotation score: 1
• Binding affinity: BindingDB: IC50=220nM,Ki=10.8nM

Gene Ontology

Molecular Function

• GO:0001614 purinergic nucleotide receptor activity
• GO:0004931 extracellularly ATP-gated monoatomic cation channel activity
• GO:0005216 monoatomic ion channel activity
• GO:0005524 ATP binding
• GO:0015267 channel activity

Biological Process

• GO:0001666 response to hypoxia
• GO:0006811 monoatomic ion transport
• GO:0006812 monoatomic cation transport
• GO:0007165 signal transduction
• GO:0007268 chemical synaptic transmission
• GO:0007274 neuromuscular synaptic transmission
• GO:0009266 response to temperature stimulus
• GO:0009408 response to heat
• GO:0009409 response to cold
• GO:0009612 response to mechanical stimulus
• GO:0009743 response to carbohydrate
• GO:0010524 positive regulation of calcium ion transport into cytosol
• GO:0014832 urinary bladder smooth muscle contraction
• GO:0030432 peristalsis
• GO:0033198 response to ATP
• GO:0034220 monoatomic ion transmembrane transport
• GO:0035590 purinergic nucleotide receptor signaling pathway
• GO:0048167 regulation of synaptic plasticity
• GO:0048266 behavioral response to pain
• GO:0050804 modulation of chemical synaptic transmission
• GO:0050850 positive regulation of calcium-mediated signaling
• GO:0050909 sensory perception of taste
• GO:0051649 establishment of localization in cell
• GO:0060079 excitatory postsynaptic potential
• GO:0070207 protein homotrimerization
• GO:0070588 calcium ion transmembrane transport
• GO:0071318 cellular response to ATP
• GO:0098655 monoatomic cation transmembrane transport
• GO:0098662 inorganic cation transmembrane transport

Cellular Component

• GO:0005886 plasma membrane
• GO:0016020 membrane
• GO:0030424 axon
• GO:0043005 neuron projection
• GO:0043235 receptor complex
• GO:0098685 Schaffer collateral - CA1 synapse
• GO:0098686 hippocampal mossy fiber to CA3 synapse
• GO:0098794 postsynapse

External links

• PDB: RCSB:5svr, PDBe:5svr, PDBj:5svr
• PDBsum: 5svr
• PubMed: 27626375
• UniProt: P56373|P2RX3_HUMAN P2X purinoceptor 3 (Gene Name=P2RX3)