8ger

E. eligens beta-glucuronidase bound to norquetiapine-glucuronide

spinqualitylabelsall models 8ger, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ger is a 1 chain structure with sequence from Lachnospira eligens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ZG5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A174ZZA3_9FIRM Publication Abstract from PubMed Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial beta-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities. Gut microbial beta-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.,Simpson JB, Walker ME, Sekela JJ, Ivey SM, Jariwala PB, Storch CM, Kowalewski ME, Graboski AL, Lietzan AD, Walton WG, Davis KA, Cloer EW, Borlandelli V, Hsiao YC, Roberts LR, Perlman DH, Liang X, Overkleeft HS, Bhatt AP, Lu K, Redinbo MR Cell Host Microbe. 2024 May 13:S1931-3128(24)00138-0. doi: , 10.1016/j.chom.2024.04.018. PMID:38754417 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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