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| | <StructureSection load='6nd3' size='340' side='right'caption='[[6nd3]], [[Resolution|resolution]] 2.36Å' scene=''> | | <StructureSection load='6nd3' size='340' side='right'caption='[[6nd3]], [[Resolution|resolution]] 2.36Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nd3]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Desag Desag]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ND3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ND3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nd3]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Oleidesulfovibrio_alaskensis_G20 Oleidesulfovibrio alaskensis G20]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ND3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ND3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTL:BETAINE+ALDEHYDE'>BTL</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]] 2.364Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cutC, Dde_3282 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=207559 DESAG])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTL:BETAINE+ALDEHYDE'>BTL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Choline_trimethylamine-lyase Choline trimethylamine-lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.99.4 4.3.99.4] </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=6nd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nd3 OCA], [https://pdbe.org/6nd3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nd3 RCSB], [https://www.ebi.ac.uk/pdbsum/6nd3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nd3 ProSAT]</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=6nd3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nd3 OCA], [http://pdbe.org/6nd3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nd3 RCSB], [http://www.ebi.ac.uk/pdbsum/6nd3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nd3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CUTC_DESAG CUTC_DESAG]] Glycine radical enzyme that catalyzes the cleavage of a C-N bond in choline, producing trimethylamine (TMA) and acetaldehyde (PubMed:23151509, PubMed:24854437). Is involved in the anaerobic choline utilization pathway that allows D.alaskensis to grow on choline as a source of carbon and energy (PubMed:23151509). Is strictly specific for choline as substrate (PubMed:24854437).<ref>PMID:23151509</ref> <ref>PMID:24854437</ref> | + | [https://www.uniprot.org/uniprot/CUTC_OLEA2 CUTC_OLEA2] Glycine radical enzyme that catalyzes the cleavage of a C-N bond in choline, producing trimethylamine (TMA) and acetaldehyde (PubMed:23151509, PubMed:24854437). Is involved in the anaerobic choline utilization pathway that allows D.alaskensis to grow on choline as a source of carbon and energy (PubMed:23151509). Is strictly specific for choline as substrate (PubMed:24854437).<ref>PMID:23151509</ref> <ref>PMID:24854437</ref> |
| | <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: Choline trimethylamine-lyase]] | |
| - | [[Category: Desag]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Oleidesulfovibrio alaskensis G20]] |
| - | [[Category: Funk, M A]] | + | [[Category: Drennan CL]] |
| - | [[Category: Barrel]] | + | [[Category: Funk MA]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Radical]]
| + | |
| Structural highlights
Function
CUTC_OLEA2 Glycine radical enzyme that catalyzes the cleavage of a C-N bond in choline, producing trimethylamine (TMA) and acetaldehyde (PubMed:23151509, PubMed:24854437). Is involved in the anaerobic choline utilization pathway that allows D.alaskensis to grow on choline as a source of carbon and energy (PubMed:23151509). Is strictly specific for choline as substrate (PubMed:24854437).[1] [2]
Publication Abstract from PubMed
The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production from choline by human gut bacterial isolates and a complex gut community. In vitro assays and a crystal structure suggest betaine aldehyde targets the gut microbial enzyme choline TMA-lyase (CutC). In our system, we do not observe activity for the previously reported CutC inhibitor 3,3-dimethylbutanol (DMB). The workflow we establish for identifying and characterizing betaine aldehyde provides a framework for developing additional inhibitors of gut microbial choline metabolism, including therapeutic candidates.
Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria.,Orman M, Bodea S, Funk MA, Campo AM, Bollenbach M, Drennan CL, Balskus EP J Am Chem Soc. 2018 Dec 17. doi: 10.1021/jacs.8b04883. PMID:30557011[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Craciun S, Balskus EP. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21307-12. doi:, 10.1073/pnas.1215689109. Epub 2012 Nov 14. PMID:23151509 doi:http://dx.doi.org/10.1073/pnas.1215689109
- ↑ Craciun S, Marks JA, Balskus EP. Characterization of choline trimethylamine-lyase expands the chemistry of glycyl radical enzymes. ACS Chem Biol. 2014 Jul 18;9(7):1408-13. doi: 10.1021/cb500113p. Epub 2014 Jun 2. PMID:24854437 doi:http://dx.doi.org/10.1021/cb500113p
- ↑ Orman M, Bodea S, Funk MA, Campo AM, Bollenbach M, Drennan CL, Balskus EP. Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria. J Am Chem Soc. 2018 Dec 17. doi: 10.1021/jacs.8b04883. PMID:30557011 doi:http://dx.doi.org/10.1021/jacs.8b04883
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