8fg8

Catalytic domain of GtfB in complex with inhibitor 2-[(2,4,5-Trihydroxyphenyl)methylidene]-1-benzofuran-3-one

spinqualitylabelsall models 8fg8, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fg8 is a 2 chain structure with sequence from Streptococcus mutans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: BTB, CA, SO4, XV5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GTFB_STRMU Production of extracellular glucans, that are thought to play a key role in the development of the dental plaque because of their ability to adhere to smooth surfaces and mediate the aggregation of bacterial cells and food debris. Publication Abstract from PubMed We designed and synthesized analogues of a previously identified biofilm inhibitor IIIC5 to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compound HA5 showed improved solubility of 120.09 mug/mL, inhibited Streptococcus mutans biofilm with an IC(50) value of 6.42 muM, and did not affect the growth of oral commensal species up to a 15-fold higher concentration. The cocrystal structure of HA5 with GtfB catalytic domain determined at 2.35 A resolution revealed its active site interactions. The ability of HA5 to inhibit S. mutans Gtfs and to reduce glucan production has been demonstrated. The hydrogel-encapsulated biofilm inhibitor (HEBI), generated by encapsulating HA5 in hydrogel, selectively inhibited S. mutans biofilms like HA5. Treatment of S. mutans-infected rats with HA5 or HEBI resulted in a significant reduction in buccal, sulcal, and proximal dental caries compared to untreated, infected rats. Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of Streptococcus mutans.,Ahirwar P, Kozlovskaya V, Nijampatnam B, Rojas EM, Pukkanasut P, Inman D, Dolmat M, Law AC, Schormann N, Deivanayagam C, Harber GJ, Michalek SM, Wu H, Kharlampieva E, Velu SE J Med Chem. 2023 Jun 7. doi: 10.1021/acs.jmedchem.3c00272. PMID:37285134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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