Structure of PDB 7bum Chain A Binding Site BS03

Receptor Information

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

PDKLKKVLDKLRLKRKDISEAAETVNKVVERLLRRMQKRESEFKGVEQLN
TGSYYEHVKISAPNEFDVMFKLEVPRIELQEYYETGAFYLVKFKRIPRGN
PLSHFLEGEVLSATKMLSKFRKIIKEEVKEIKDIDVSVEKEKPGSPAVTL
LIRNPEEISVDIILALESKGSWPISTKEGLPIQGWLGTKVRTNLRREPFY
LVPKNAKDGNSFQGETWRLSFSHTEKYILNNHGIEKTCCESSGAKCCRKE
CLKLMKYLLEQLKKEFQELDAFCSYHVKTAIFHMWTQDPQDSQWDPRNLS
SCFDKLLAFFLECLRTEKLDHYFIPKFNLFSQELIDRKSKEFLSKKIEYE
RNNGFPIFDKL

Ligand information

• Ligand ID: 5GP
• InChI: InChI=1S/C10H14N5O8P/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(23-9)1-22-24(19,20)21/h2-3,5-6,9,16-17H,1H2,(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
• InChIKey: RQFCJASXJCIDSX-UUOKFMHZSA-N
• SMILES:
  CACTVS 3.341: NC1=Nc2n(cnc2C(=O)N1)[C@@H]3O[C@H](CO[P](O)(O)=O)[C@@H](O)[C@H]3O
  CACTVS 3.341: NC1=Nc2n(cnc2C(=O)N1)[CH]3O[CH](CO[P](O)(O)=O)[CH](O)[CH]3O
  ACDLabs 10.04: O=C1c2ncn(c2N=C(N)N1)C3OC(C(O)C3O)COP(=O)(O)O
  OpenEye OEToolkits 1.5.0: c1nc2c(n1C3C(C(C(O3)COP(=O)(O)O)O)O)N=C(NC2=O)N
  OpenEye OEToolkits 1.5.0: c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)N=C(NC2=O)N
• Formula: C10 H14 N5 O8 P
• Name: GUANOSINE-5'-MONOPHOSPHATE
• ChEMBL: CHEMBL283807
• DrugBank: DB01972
• ZINC: ZINC000002159505
• PDB chain: 7bum Chain A Residue 603

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): D213 S291 I309 K350 R364
• Binding residue (residue number reindexed from 1): D67 S145 I163 K204 R218
• Annotation score: 3

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)