6hl9
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6hl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HL9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6hl9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HL9 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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]] 2.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=6hl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl9 OCA], [https://pdbe.org/6hl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hl9 RCSB], [https://www.ebi.ac.uk/pdbsum/6hl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl9 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=6hl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl9 OCA], [https://pdbe.org/6hl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hl9 RCSB], [https://www.ebi.ac.uk/pdbsum/6hl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/GLAH_ECOLI GLAH_ECOLI] Acts as an alpha-ketoglutarate-dependent dioxygenase catalyzing hydroxylation of glutarate (GA) to L-2-hydroxyglutarate (L2HG) in the stationary phase of E.coli. Functions in a L-lysine degradation pathway that proceeds via cadaverine, glutarate and L-2-hydroxyglutarate. Other dicarboxylic acids (oxalate, malonate, succinate, adipate, and pimelate) are not substrates for this enzyme.<ref>PMID:30498244</ref> | [https://www.uniprot.org/uniprot/GLAH_ECOLI GLAH_ECOLI] Acts as an alpha-ketoglutarate-dependent dioxygenase catalyzing hydroxylation of glutarate (GA) to L-2-hydroxyglutarate (L2HG) in the stationary phase of E.coli. Functions in a L-lysine degradation pathway that proceeds via cadaverine, glutarate and L-2-hydroxyglutarate. Other dicarboxylic acids (oxalate, malonate, succinate, adipate, and pimelate) are not substrates for this enzyme.<ref>PMID:30498244</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Lysine degradation has remained elusive in many organisms including Escherichia coli. Here we report catabolism of lysine to succinate in E. coli involving glutarate and L-2-hydroxyglutarate as intermediates. We show that CsiD acts as an alpha-ketoglutarate-dependent dioxygenase catalysing hydroxylation of glutarate to L-2-hydroxyglutarate. CsiD is found widespread in bacteria. We present crystal structures of CsiD in complex with glutarate, succinate, and the inhibitor N-oxalyl-glycine, demonstrating strong discrimination between the structurally related ligands. We show that L-2-hydroxyglutarate is converted to alpha-ketoglutarate by LhgO acting as a membrane-bound, ubiquinone-linked dehydrogenase. Lysine enters the pathway via 5-aminovalerate by the promiscuous enzymes GabT and GabD. We demonstrate that repression of the pathway by CsiR is relieved upon glutarate binding. In conclusion, lysine degradation provides an important link in central metabolism. Our results imply the gut microbiome as a potential source of glutarate and L-2-hydroxyglutarate associated with human diseases such as cancer and organic acidurias. | ||
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| - | Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate.,Knorr S, Sinn M, Galetskiy D, Williams RM, Wang C, Muller N, Mayans O, Schleheck D, Hartig JS Nat Commun. 2018 Nov 29;9(1):5071. doi: 10.1038/s41467-018-07563-6. PMID:30498244<ref>PMID:30498244</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 6hl9" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
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