View source for 8fg8


==Catalytic domain of GtfB in complex with inhibitor 2-[(2,4,5-Trihydroxyphenyl)methylidene]-1-benzofuran-3-one==
<StructureSection load='8fg8' size='340' side='right'caption='[[8fg8]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fg8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_mutans Streptococcus mutans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FG8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XV5:(2Z)-2-[(2,4,5-trihydroxyphenyl)methylidene]-1-benzofuran-3(2H)-one'>XV5</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8fg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fg8 OCA], [https://pdbe.org/8fg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fg8 RCSB], [https://www.ebi.ac.uk/pdbsum/8fg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fg8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GTFB_STRMU 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.
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== 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<ref>PMID:37285134</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fg8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus mutans]]
[[Category: Deivanayagam C]]
[[Category: Schormann N]]
[[Category: Velu S]]