6hl9 - Revision history

OCA at 07:49, 7 February 2024

OCA — Wed, 07 Feb 2024 07:49:15 GMT

←Older revision		Revision as of 07:49, 7 February 2024
Line 4:		Line 4:
	== 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.
-
-	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>
-
-	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/>

OCA at 06:53, 8 February 2023

OCA — Wed, 08 Feb 2023 06:53:29 GMT

←Older revision		Revision as of 06:53, 8 February 2023
Line 1:		Line 1:

	==Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate==		==Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate==
-	<StructureSection load='6hl9' size='340' side='right' caption='[[6hl9]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='6hl9' size='340' side='right'caption='[[6hl9]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hl9]] is a 2 chain structure. 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 [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/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"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene></td></tr>	+	</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6hl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl9 OCA], [~~http~~://pdbe.org/6hl9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6hl9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6hl9 PDBsum], [~~http~~://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 ==
-	[~~[http~~://www.uniprot.org/uniprot/~~A0A1X3JCQ2_ECOLX A0A1X3JCQ2_ECOLX~~]~~] May be involved~~ in the ~~control~~ of ~~utilization of gamma-aminobutyric acid~~.~~[HAMAP~~-~~Rule~~:~~MF_01083]~~	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hartig, J S~~]]	+	[[Category: Escherichia coli K-12]]
-	[[Category: ~~Mayans, O~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Williams, R M~~]]	+	[[Category: Hartig JS]]
-	[[Category: ~~Alpha-ketoglutarate-dependent~~]]	+	[[Category: Mayans O]]
-	[[Category: ~~Glutarate hydroxylase]]~~	+	[[Category: Williams RM]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Jelly roll~~]]	+

OCA at 06:45, 21 February 2019

OCA — Thu, 21 Feb 2019 06:45:12 GMT

←Older revision		Revision as of 06:45, 21 February 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hl9 is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate==
		+	<StructureSection load='6hl9' size='340' side='right' caption='[[6hl9]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hl9]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HL9 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hl9 OCA], [http://pdbe.org/6hl9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hl9 RCSB], [http://www.ebi.ac.uk/pdbsum/6hl9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hl9 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A0A1X3JCQ2_ECOLX A0A1X3JCQ2_ECOLX]] May be involved in the control of utilization of gamma-aminobutyric acid.[HAMAP-Rule:MF_01083]
		+	<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.

-	~~Authors: Williams, R~~.M., ~~Mayans~~, O., ~~Hartig~~, J.S.	+	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>

-	~~Description: Crystal Structure~~ of the ~~CsiD Glutarate Hydroxylase in complex with Succinate~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: Hartig, J.S]]	+	<div class="pdbe-citations 6hl9" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hartig, J S]]
	[[Category: Mayans, O]]		[[Category: Mayans, O]]
-	[[Category: Williams, R.M]]	+	[[Category: Williams, R M]]
		+	[[Category: Alpha-ketoglutarate-dependent]]
		+	[[Category: Glutarate hydroxylase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Jelly roll]]

OCA at 05:59, 30 January 2019

OCA — Wed, 30 Jan 2019 05:59:41 GMT

←Older revision		Revision as of 05:59, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hl9 is ON HOLD	+	The entry 6hl9 is ON HOLD until Paper Publication

	Authors: Williams, R.M., Mayans, O., Hartig, J.S.		Authors: Williams, R.M., Mayans, O., Hartig, J.S.
Line 7:		Line 7:
	Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate		Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Hartig, J.S]]
	[[Category: Mayans, O]]		[[Category: Mayans, O]]
	[[Category: Williams, R.M]]		[[Category: Williams, R.M]]
-	[[Category: Hartig, J.S]]

OCA at 10:20, 16 January 2019

OCA — Wed, 16 Jan 2019 10:20:32 GMT

←Older revision		Revision as of 10:20, 16 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hl9 is ON HOLD ~~until Paper Publication~~	+	The entry 6hl9 is ON HOLD

	Authors: Williams, R.M., Mayans, O., Hartig, J.S.		Authors: Williams, R.M., Mayans, O., Hartig, J.S.
Line 7:		Line 7:
	Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate		Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Hartig, J.S]]
	[[Category: Mayans, O]]		[[Category: Mayans, O]]
	[[Category: Williams, R.M]]		[[Category: Williams, R.M]]
		+	[[Category: Hartig, J.S]]

OCA at 06:10, 26 September 2018

OCA — Wed, 26 Sep 2018 06:10:24 GMT

←Older revision		Revision as of 06:10, 26 September 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6hl9 is ON HOLD	+	The entry 6hl9 is ON HOLD until Paper Publication

	Authors: Williams, R.M., Mayans, O., Hartig, J.S.		Authors: Williams, R.M., Mayans, O., Hartig, J.S.
Line 7:		Line 7:
	Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate		Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Mayans, O]]
	[[Category: Hartig, J.S]]		[[Category: Hartig, J.S]]
		+	[[Category: Mayans, O]]
	[[Category: Williams, R.M]]		[[Category: Williams, R.M]]

OCA: Protected "6hl9" [edit=sysop:move=sysop]

OCA — Wed, 19 Sep 2018 18:10:48 GMT

Protected "6hl9" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:10, 19 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hl9 is ON HOLD Authors: Williams, R.M., Mayans, O., Hartig, J.S. Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with ...

OCA — Wed, 19 Sep 2018 18:10:46 GMT

New page: '''Unreleased structure''' The entry 6hl9 is ON HOLD Authors: Williams, R.M., Mayans, O., Hartig, J.S. Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with ...

New page

'''Unreleased structure'''

The entry 6hl9 is ON HOLD

Authors: Williams, R.M., Mayans, O., Hartig, J.S.

Description: Crystal Structure of the CsiD Glutarate Hydroxylase in complex with Succinate
[[Category: Unreleased Structures]]
[[Category: Mayans, O]]
[[Category: Hartig, J.S]]
[[Category: Williams, R.M]]