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| | <StructureSection load='6ufy' size='340' side='right'caption='[[6ufy]], [[Resolution|resolution]] 2.71Å' scene=''> | | <StructureSection load='6ufy' size='340' side='right'caption='[[6ufy]], [[Resolution|resolution]] 2.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ufy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UFY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UFY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ufy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UFY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BT_2086 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=226186 BACTN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ufy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufy OCA], [http://pdbe.org/6ufy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ufy RCSB], [http://www.ebi.ac.uk/pdbsum/6ufy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufy ProSAT]</span></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=6ufy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ufy OCA], [https://pdbe.org/6ufy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ufy RCSB], [https://www.ebi.ac.uk/pdbsum/6ufy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ufy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8A600_BACTN Q8A600_BACTN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bactn]] | + | [[Category: Bacteroides thetaiotaomicron VPI-5482]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Seegar, T C.M]] | + | [[Category: Seegar TCM]] |
| - | [[Category: Bile salt hydrolase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
Q8A600_BACTN
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Development of a covalent inhibitor of gut bacterial bile salt hydrolases. Nat Chem Biol. 2020 Mar;16(3):318-326. doi: 10.1038/s41589-020-0467-3. Epub 2020 , Feb 10. PMID:32042200 doi:http://dx.doi.org/10.1038/s41589-020-0467-3
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