Structure of PDB 7bum Chain B Binding Site BS02

Receptor Information

>7bum Chain B (length=361) Species: 10090 (Mus musculus)

PDKLKKVLDKLRLKRKDISEAAETVNKVVERLLRRMQKRESEFKGVEQLN
TGSYYEHVKISAPNEFDVMFKLEVPRIELQEYYETGAFYLVKFKRIPRGN
PLSHFLEGEVLSATKMLSKFRKIIKEEVKEIKDIDVSVEKEKPGSPAVTL
LIRNPEEISVDIILALESKGSWPISTKEGLPIQGWLGTKVRTNLRREPFY
LVPKNAKDGNSFQGETWRLSFSHTEKYILNNHGIEKTCCESSGAKCCRKE
CLKLMKYLLEQLKKEFQELDAFCSYHVKTAIFHMWTQDPQDSQWDPRNLS
SCFDKLLAFFLECLRTEKLDHYFIPKFNLFSQELIDRKSKEFLSKKIEYE
RNNGFPIFDKL

Ligand information

• Ligand ID: A
• InChI: InChI=1S/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1
• InChIKey: UDMBCSSLTHHNCD-KQYNXXCUSA-N
• SMILES:
  CACTVS 3.341: Nc1ncnc2n(cnc12)[CH]3O[CH](CO[P](O)(O)=O)[CH](O)[CH]3O
  CACTVS 3.341: Nc1ncnc2n(cnc12)[C@@H]3O[C@H](CO[P](O)(O)=O)[C@@H](O)[C@H]3O
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)N
  ACDLabs 10.04: O=P(O)(O)OCC3OC(n2cnc1c(ncnc12)N)C(O)C3O
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(O)O)O)O)N
• Formula: C10 H14 N5 O7 P
• Name: ADENOSINE-5'-MONOPHOSPHATE
• ChEMBL: CHEMBL752
• DrugBank: DB00131
• ZINC: ZINC000003860156
• PDB chain: 7bum Chain B Residue 602

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7bum Mn2+Directly Activates cGAS and Structural Analysis Suggests Mn2+Induces a Noncanonical Catalytic Synthesis of 2'3'-cGAMP.
• Resolution: 3.047 Å
• Binding residue (original residue number in PDB): R364 C419 Y421
• Binding residue (residue number reindexed from 1): R218 C273 Y275
• Annotation score: 4

Enzymatic activity

• Enzyme Commision number: 2.7.7.86: cyclic GMP-AMP synthase.

Gene Ontology

Molecular Function

• GO:0003677 DNA binding
• GO:0003682 chromatin binding
• GO:0003690 double-stranded DNA binding
• GO:0005515 protein binding
• GO:0005524 ATP binding
• GO:0005525 GTP binding
• GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
• GO:0008289 lipid binding
• GO:0016779 nucleotidyltransferase activity
• GO:0031491 nucleosome binding
• GO:0042803 protein homodimerization activity
• GO:0046872 metal ion binding
• GO:0061501 2',3'-cyclic GMP-AMP synthase activity
• GO:0140693 molecular condensate scaffold activity
• GO:0160004 poly-ADP-D-ribose modification-dependent protein binding

Biological Process

• GO:0002218 activation of innate immune response
• GO:0002221 pattern recognition receptor signaling pathway
• GO:0002230 positive regulation of defense response to virus by host
• GO:0002637 regulation of immunoglobulin production
• GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
• GO:0006281 DNA repair
• GO:0006974 DNA damage response
• GO:0008340 determination of adult lifespan
• GO:0019933 cAMP-mediated signaling
• GO:0019934 cGMP-mediated signaling
• GO:0032479 regulation of type I interferon production
• GO:0032481 positive regulation of type I interferon production
• GO:0038001 paracrine signaling
• GO:0045087 innate immune response
• GO:0045738 negative regulation of DNA repair
• GO:0050776 regulation of immune response
• GO:0050863 regulation of T cell activation
• GO:0051607 defense response to virus
• GO:0071360 cellular response to exogenous dsRNA
• GO:0140896 cGAS/STING signaling pathway
• GO:0160049 negative regulation of cGAS/STING signaling pathway
• GO:2000042 negative regulation of double-strand break repair via homologous recombination
• GO:2000774 positive regulation of cellular senescence

Cellular Component

• GO:0005634 nucleus
• GO:0005654 nucleoplasm
• GO:0005694 chromosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005886 plasma membrane
• GO:0016604 nuclear body
• GO:0035861 site of double-strand break

External links

• PDB: RCSB:7bum, PDBe:7bum, PDBj:7bum
• PDBsum: 7bum
• PubMed: 32814054
• UniProt: Q8C6L5|CGAS_MOUSE Cyclic GMP-AMP synthase (Gene Name=Cgas)