Structure of PDB 7yq8 Chain A Binding Site BS04

Receptor Information

>7yq8 Chain A (length=730) Species: 9606 (Homo sapiens)

KGIPKLDDANDAGGKHSLECTLILTEGDSAKSLAVSGLGVIGRDRYGVFP
LRGKILNVREASHKQIMENAEINNIIKIVGLQYKKSYDDAESLKTLRYGK
IMIMTDQDQDGSHIKGLLINFIHHNWPSLLKHGFLEEFITPIVKASKNKQ
ELSFYSIPEFDEWKKHIENQKAWKIKYYKGLGTSTAKEAKEYFADMERHR
ILFRYAGPEDDAAITLAFSKKKIDDRKEWLTNFMEDRRQRRLHGLPEQFL
YGTATKHLTYNDFINKELILFSNSDNERSIPSLVDGFKPGQRKVLFTCFK
RNDKREVKVAQLAGSVAEMSAYHHGEQALMMTIVNLAQNFVGSNNINLLQ
PIGQFGTRLHGGKDAASPRYIFTMLSTLARLLFPAVDDNLLKFLYDDNQR
VEPEWYIPIIPMVLINGAEGIGTGWACKLPNYDAREIVNNVRRMLDGLDP
HPMLPNYKNFKGTIQELGQNQYAVSGEIFVVDRNTVEITELPVRTWTQVY
KEQVLEPMLNGTDKTPALISDYKEYHTDTTVKFVVKMTEEKLAQAEAAGL
HKVFKLQTTLTCNSMVLFDHMGCLKKYETVQDILKEFFDLRLSYYGLRKE
WLVGMLGAESTKLNNQARFILEKIQGKITIENRSKKDLIQMLVQRGYESD
PVKAWKEAQEKAGPDFNYILNMSLWSLTKEKVEELIKQRDAKGREVNDLK
RKSPSDLWKEDLAAFVEELDKVESQEREDV

Ligand information

• Ligand ID: EVP
• InChI: InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
• InChIKey: VJJPUSNTGOMMGY-MRVIYFEKSA-N
• SMILES:
  CACTVS 3.370: COc1cc(cc(OC)c1O)[C@H]2[C@@H]3[C@H](COC3=O)[C@H](O[C@@H]4O[C@@H]5CO[C@@H](C)O[C@H]5[C@H](O)[C@H]4O)c6cc7OCOc7cc26
  OpenEye OEToolkits 1.7.2: CC1OCC2C(O1)C(C(C(O2)OC3c4cc5c(cc4C(C6C3COC6=O)c7cc(c(c(c7)OC)O)OC)OCO5)O)O
  OpenEye OEToolkits 1.7.2: C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@@H]3c4cc5c(cc4[C@H]([C@@H]6[C@@H]3COC6=O)c7cc(c(c(c7)OC)O)OC)OCO5)O)O
  ACDLabs 12.01: O=C1OCC7C1C(c2cc(OC)c(O)c(OC)c2)c4cc3OCOc3cc4C7OC6OC5C(OC(OC5)C)C(O)C6O
  CACTVS 3.370: COc1cc(cc(OC)c1O)[CH]2[CH]3[CH](COC3=O)[CH](O[CH]4O[CH]5CO[CH](C)O[CH]5[CH](O)[CH]4O)c6cc7OCOc7cc26
• Formula: C29 H32 O13
• Name: (5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol -5-yl 4,6-O-[(1R)-ethylidene]-beta-D-glucopyranoside;
  Etoposide;
  VP-16
• ChEMBL: CHEMBL44657
• DrugBank: DB00773
• ZINC: ZINC000003938684
• PDB chain: 7yq8 Chain F Residue 101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7yq8 ERK2-topoisomerase II regulatory axis is important for gene activation in immediate early genes.
• Resolution: 3.9 Å
• Binding residue (original residue number in PDB): G483 R508 M787
• Binding residue (residue number reindexed from 1): G27 R52 M331
• Annotation score: 1

Enzymatic activity

• Enzyme Commision number: 5.6.2.2: DNA topoisomerase (ATP-hydrolyzing).

Gene Ontology

Molecular Function

• GO:0003677 DNA binding
• GO:0003682 chromatin binding
• GO:0003916 DNA topoisomerase activity
• GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0043021 ribonucleoprotein complex binding
• GO:0046872 metal ion binding

Biological Process

• GO:0000712 resolution of meiotic recombination intermediates
• GO:0000819 sister chromatid segregation
• GO:0001764 neuron migration
• GO:0006259 DNA metabolic process
• GO:0006265 DNA topological change
• GO:0007409 axonogenesis
• GO:0030183 B cell differentiation
• GO:0030900 forebrain development
• GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
• GO:0060255 regulation of macromolecule metabolic process
• GO:0070301 cellular response to hydrogen peroxide
• GO:0071318 cellular response to ATP
• GO:0090398 cellular senescence
• GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining

Cellular Component

• GO:0000792 heterochromatin
• GO:0005634 nucleus
• GO:0005654 nucleoplasm
• GO:0005730 nucleolus
• GO:0005829 cytosol
• GO:1990904 ribonucleoprotein complex

External links

• PDB: RCSB:7yq8, PDBe:7yq8, PDBj:7yq8
• PDBsum: 7yq8
• PubMed: 38097570
• UniProt: Q02880|TOP2B_HUMAN DNA topoisomerase 2-beta (Gene Name=TOP2B)