|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6uh4' size='340' side='right'caption='[[6uh4]], [[Resolution|resolution]] 3.51Å' scene=''> | | <StructureSection load='6uh4' size='340' side='right'caption='[[6uh4]], [[Resolution|resolution]] 3.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uh4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_thetaiotaomicron"_distaso_1912 "bacillus thetaiotaomicron" distaso 1912]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UH4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uh4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UH4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QC7:(5R,6R)-6-[(1S,2R,4aS,4bS,7R,8aS,10R,10aS)-7,10-dihydroxy-1,2,4b-trimethyltetradecahydrophenanthren-2-yl]-5-methylheptan-2-one'>QC7</scene></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]] 3.51Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ufy|6ufy]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QC7:(5R,6R)-6-[(1S,2R,4aS,4bS,7R,8aS,10R,10aS)-7,10-dihydroxy-1,2,4b-trimethyltetradecahydrophenanthren-2-yl]-5-methylheptan-2-one'>QC7</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cbh_1, Btheta7330_00957, SAMN02910322_01222 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=818 "Bacillus thetaiotaomicron" Distaso 1912])</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=6uh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uh4 OCA], [https://pdbe.org/6uh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uh4 RCSB], [https://www.ebi.ac.uk/pdbsum/6uh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uh4 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Choloylglycine_hydrolase Choloylglycine hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.24 3.5.1.24] </span></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=6uh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uh4 OCA], [http://pdbe.org/6uh4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uh4 RCSB], [http://www.ebi.ac.uk/pdbsum/6uh4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uh4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0P0ENF5_BACT4 A0A0P0ENF5_BACT4] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6uh4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6uh4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus thetaiotaomicron distaso 1912]] | + | [[Category: Bacteroides thetaiotaomicron]] |
| - | [[Category: Choloylglycine hydrolase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Seegar, T C.M]] | + | [[Category: Seegar TCM]] |
| - | [[Category: Bile salt hydrolase b. theta]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
|
