Structure of PDB 8ouo Chain A Binding Site BS02

Receptor Information

>8ouo Chain A (length=648) Species: 9606 (Homo sapiens)

GAAARWDLCIDQAVVFIEDAIQYRSINHRVDASSMWLYRRYYSNVCQRTL
SFTIFLILFLAFIETPSSLTSTADVRYRAAPWEPPCGLTESVEVLCLLVF
AADLSVKGYLFGWAHFQKNLWLLGYLVVLVVSLVDWTVSLSLVCHEPLRI
RRLLRPFFLLQNSSMMKKTLKCIRWSLPEMASVGLLLAIHLCLFTMFGML
LFAGGKQDDGQDRERLTYFQNLPESLTSLLVLLTTANNPDVMIPAYSKNR
AYAIFFIVFTVIGSLFLMNLLTAIIYSQFRGYLMKSLQTSLFRRRLGTRA
AFEVLSSMVGAVGVKPQNLLQVLQKVQLDSSHKQAMMEKVRSYGSVLLSA
EEFQKLFNELDRSVVKEHPPRPEYQSPFLQSAQFLFGHYYFDYLGNLIAL
ANLVSICVFLVLDADVLPAERDDFILGILNCVFIVYYLLEMLLKVFALGL
RGYLSYPSNVFDGLLTVVLLVLEISTLAVYRLPHPGWRPEMVGLLSLWDM
TRMLNMLIVFRFLRIIPSMKPMAVVASTVLGLVQNMRAFGGILVVVYYVF
AIIGINLFRGVIVALPSAPCGSFEQLEYWANNFDDFAAALVTLWNLMVVN
NWQVFLDAYRRYSGPWSKIYFVLWWLVSSVIWVNLFLALILENFLHKW

Ligand information

• Ligand ID: W4E
• InChI: InChI=1S/C30H29NO3/c1-31-18-17-23-20-29(32-2)30(34-25-11-7-4-8-12-25)21-27(23)28(31)19-22-13-15-26(16-14-22)33-24-9-5-3-6-10-24/h3-16,20-21,28H,17-19H2,1-2H3/t28-/m0/s1
• InChIKey: BTNHPUSFPKFAPU-NDEPHWFRSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: CN1CCc2cc(c(cc2C1Cc3ccc(cc3)Oc4ccccc4)Oc5ccccc5)OC
  CACTVS 3.385: COc1cc2CCN(C)[C@@H](Cc3ccc(Oc4ccccc4)cc3)c2cc1Oc5ccccc5
  OpenEye OEToolkits 2.0.7: CN1CCc2cc(c(cc2[C@@H]1Cc3ccc(cc3)Oc4ccccc4)Oc5ccccc5)OC
  CACTVS 3.385: COc1cc2CCN(C)[CH](Cc3ccc(Oc4ccccc4)cc3)c2cc1Oc5ccccc5
• Formula: C30 H29 N O3
• Name: (1S)-6-methoxy-2-methyl-7-phenoxy-1-[(4-phenoxyphenyl)methyl]-3,4-dihydro-1H-isoquinoline;
  SG-094
• PDB chain: 8ouo Chain A Residue 803

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8ouo Structural basis for inhibition of the lysosomal two-pore channel TPC2 by a small molecule antagonist.
• Resolution: 3.0 Å
• Binding residue (original residue number in PDB): D435 Y436 N439 F555 I558 S561
• Binding residue (residue number reindexed from 1): D392 Y393 N396 F512 I515 S518
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0005245 voltage-gated calcium channel activity
• GO:0005248 voltage-gated sodium channel activity
• GO:0005262 calcium channel activity
• GO:0005515 protein binding
• GO:0015280 ligand-gated sodium channel activity
• GO:0019901 protein kinase binding
• GO:0042802 identical protein binding
• GO:0072345 NAADP-sensitive calcium-release channel activity
• GO:0080025 phosphatidylinositol-3,5-bisphosphate binding
• GO:0097682 intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity

Biological Process

• GO:0006874 intracellular calcium ion homeostasis
• GO:0006939 smooth muscle contraction
• GO:0007040 lysosome organization
• GO:0010506 regulation of autophagy
• GO:0017157 regulation of exocytosis
• GO:0019065 receptor-mediated endocytosis of virus by host cell
• GO:0019722 calcium-mediated signaling
• GO:0033280 response to vitamin D
• GO:0034220 monoatomic ion transmembrane transport
• GO:0035725 sodium ion transmembrane transport
• GO:0048086 negative regulation of developmental pigmentation
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051452 intracellular pH reduction
• GO:0070588 calcium ion transmembrane transport
• GO:0075509 endocytosis involved in viral entry into host cell
• GO:0090117 endosome to lysosome transport of low-density lipoprotein particle

Cellular Component

• GO:0005764 lysosome
• GO:0005765 lysosomal membrane
• GO:0005768 endosome
• GO:0005829 cytosol
• GO:0010008 endosome membrane
• GO:0016020 membrane
• GO:0031902 late endosome membrane
• GO:0033162 melanosome membrane
• GO:0034702 monoatomic ion channel complex
• GO:0036020 endolysosome membrane

External links

• PDB: RCSB:8ouo, PDBe:8ouo, PDBj:8ouo
• PDBsum: 8ouo
• PubMed: 38815576
• UniProt: Q8NHX9|TPC2_HUMAN Two pore channel protein 2 (Gene Name=TPCN2)