6uh4

B. theta Bile Salt Hydrolase with covalent inhibitor

spinqualitylabelsall models 6uh4, resolution 3.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uh4 is a 4 chain structure with sequence from Bacteroides thetaiotaomicron. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.51Å Ligands: QC7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0P0ENF5_BACT4 Publication Abstract from PubMed Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria to study the effects of bile acids on host physiology. Here, we report the development of a covalent pan-inhibitor of gut bacterial BSHs. From a rationally designed candidate library, we identified a lead compound bearing an alpha-fluoromethyl ketone warhead that modifies BSH at the catalytic cysteine residue. This inhibitor abolished BSH activity in conventional mouse feces. Mice gavaged with a single dose of this compound displayed decreased BSH activity and decreased deconjugated bile acid levels in feces. Our studies demonstrate the potential of a covalent BSH inhibitor to modulate bile acid composition in vivo. Development of a covalent inhibitor of gut bacterial bile salt hydrolases.,Adhikari AA, Seegar TCM, Ficarro SB, McCurry MD, Ramachandran D, Yao L, Chaudhari SN, Ndousse-Fetter S, Banks AS, Marto JA, Blacklow SC, Devlin AS Nat Chem Biol. 2020 Mar;16(3):318-326. doi: 10.1038/s41589-020-0467-3. Epub 2020 , Feb 10. PMID:32042200 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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