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| - | ==E491Q mutant of choline TMA-lyase== | + | ==T502A mutant of choline TMA-lyase== |
| - | <StructureSection load='5faw' size='340' side='right' caption='[[5faw]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='5faw' size='340' side='right'caption='[[5faw]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5faw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FAW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5faw]] is a 2 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=5FAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FAW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.852Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fau|5fau]], [[5fav|5fav]], [[5fay|5fay]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5faw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5faw OCA], [https://pdbe.org/5faw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5faw RCSB], [https://www.ebi.ac.uk/pdbsum/5faw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5faw 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=5faw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5faw OCA], [http://pdbe.org/5faw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5faw RCSB], [http://www.ebi.ac.uk/pdbsum/5faw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5faw 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: Large Structures]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Oleidesulfovibrio alaskensis G20]] |
| - | [[Category: Funk, M A]] | + | [[Category: Drennan CL]] |
| - | [[Category: Lyase]] | + | [[Category: Funk MA]] |
| - | [[Category: Mutant]]
| + | |
| - | [[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
Deamination of choline catalyzed by the glycyl radical enzyme choline trimethylamine-lyase (CutC) has emerged as an important route for the production of trimethylamine, a microbial metabolite associated with both human disease and biological methane production. Here, we have determined five high-resolution X-ray structures of wild-type CutC and mechanistically informative mutants in the presence of choline. Within an unexpectedly polar active site, CutC orients choline through hydrogen bonding with a putative general base, and through close interactions between phenolic and carboxylate oxygen atoms of the protein scaffold and the polarized methyl groups of the trimethylammonium moiety. These structural data, along with biochemical analysis of active site mutants, support a mechanism that involves direct elimination of trimethylamine. This work broadens our understanding of radical-based enzyme catalysis and will aid in the rational design of inhibitors of bacterial trimethylamine production.
Molecular Basis of C-N Bond Cleavage by the Glycyl Radical Enzyme Choline Trimethylamine-Lyase.,Bodea S, Funk MA, Balskus EP, Drennan CL Cell Chem Biol. 2016 Sep 23. pii: S2451-9456(16)30287-2. doi:, 10.1016/j.chembiol.2016.07.020. PMID:27642068[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
- ↑ Bodea S, Funk MA, Balskus EP, Drennan CL. Molecular Basis of C-N Bond Cleavage by the Glycyl Radical Enzyme Choline Trimethylamine-Lyase. Cell Chem Biol. 2016 Sep 23. pii: S2451-9456(16)30287-2. doi:, 10.1016/j.chembiol.2016.07.020. PMID:27642068 doi:http://dx.doi.org/10.1016/j.chembiol.2016.07.020
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