Fig. 4

Shared and microbial-specific drug metabolism by human and gut microbes. a Shared metabolism of triptan drugs by human and microbial Tryptophan 2,3-dioxygenase (TRPO2, EC 1.13.11.11). b Molecular similarity network (MSN) of triptan drugs such as sumatriptan, zolmitriptan, and melatonin. c Protein sequence similarity network (SSN) of bacterial TRPO2. d Three different structural alignments of diverse microbial TRPO2 monomeric models and human TRPO2 (PDB: 5TIA), including the predicted binding mode of rizatriptan (red sticks) by molecular docking in the context of the HEME cofactor (gray sticks). e Microbial-specific metabolism by microbial aryl-dialkyl phosphate hydrolase (ADAPH, EC 3.1.8.1). f MSN of aryl alcohol–containing drugs, such as acetaminophen, salicylic acid, and guaiacol. g Protein SSN of ADAPH. h Three different structural alignments of diverse microbial ADAPH monomeric models against the ADAPH from Bacillus cereus (PDB: 2IOF), including the crystallographic mode of a phosphate ion (red spheres) in the context of the Mg²⁺ cofactor (cyan sphere). In the MSNs, edge size corresponds to the similarity between molecules at a 50% cutoff for constructing the trees. The SSN for both proteins was constructed using a 70% sequence similarity. Nodes and protein structures are colored according to phylum. The maximum common substructure of the drugs is colored in red