6jz5 | pdb_00006jz5

b-glucuronidase from Ruminococcus gnavus in complex with D-glucuronic acid

spinqualitylabelsall models 6jz5, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6jz5 is a 2 chain structure with sequence from Ruminococcus gnavus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: BDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6W7J7_RUMGN Publication Abstract from PubMed Selective inhibitors of gut bacterial beta-glucuronidases (GUSs) are of particular interest in the prevention of xenobiotic-induced toxicities. This study reports the first structure-activity relationships on potency and selectivity of several iminocyclitols (2-7) for the GUSs. Complex structures of Ruminococcus gnavus GUS with 2-7 explained how charge, conformation, and substituent of iminocyclitols affect their potency and selectivity. N1 of uronic isofagomine (2) made strong electrostatic interactions with two catalytic glutamates of GUSs, resulting in the most potent inhibition (Ki >/= 11 nM). C6-propyl analogue of 2 (6) displayed 700-fold selectivity for opportunistic bacterial GUSs (Ki = 74 nM for E. coli GUS and 51.8 muM for RgGUS). In comparison with 2, there was 200-fold enhancement in the selectivity, which was attributed to differential interactions between the propyl group and loop 5 residues of the GUSs. The results provide useful insights to develop potent and selective inhibitors for undesired GUSs. Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes.,Dashnyam P, Lin HY, Chen CY, Gao S, Yeh LF, Hsieh WC, Tu Z, Lin CH J Med Chem. 2020 May 14;63(9):4617-4627. doi: 10.1021/acs.jmedchem.9b01918. Epub , 2020 Mar 9. PMID:32105467 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glucuronisidase 3D structures

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