6nd3: Difference between revisions
New page: '''Unreleased structure''' The entry 6nd3 is ON HOLD Authors: Funk, M.A., Drennan, C.L. Description: wild-type choline TMA lyase in complex with betaine aldehyde [[Category: Unreleased... |
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The | ==wild-type choline TMA lyase in complex with betaine aldehyde== | ||
<StructureSection load='6nd3' size='340' side='right'caption='[[6nd3]], [[Resolution|resolution]] 2.36Å' scene=''> | |||
== Structural highlights == | |||
<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='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='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='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> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:30557011</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6nd3" style="background-color:#fffaf0;"></div> | ||
[[Category: Drennan | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Oleidesulfovibrio alaskensis G20]] | |||
[[Category: Drennan CL]] | |||
[[Category: Funk MA]] | |||
Latest revision as of 09:49, 11 October 2023
wild-type choline TMA lyase in complex with betaine aldehydewild-type choline TMA lyase in complex with betaine aldehyde
Structural highlights
FunctionCUTC_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 PubMedThe 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
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