2cw6 - Revision history

OCA at 13:44, 13 March 2024

OCA — Wed, 13 Mar 2024 13:44:04 GMT

←Older revision		Revision as of 13:44, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='2cw6' size='340' side='right'caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2cw6' size='340' side='right'caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=3HG:3~~-~~HYDROXYPENTANEDIOIC+ACID'>3HG</scene>~~, ~~<scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.1Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[https:~~/~~/en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase]~~, ~~with EC number [https~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [https://pdbe.org/2cw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [https://www.ebi.ac.uk/pdbsum/2cw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cw6 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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [https://pdbe.org/2cw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [https://www.ebi.ac.uk/pdbsum/2cw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cw6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[https://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>	+	[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[https://omim.org/entry/246450 246450]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref> <ref>PMID:22865860</ref> <ref>PMID:22847177</ref>	+	[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref> <ref>PMID:22865860</ref> <ref>PMID:22847177</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cw6 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cw6 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase is a key enzyme in the ketogenic pathway that supplies metabolic fuel to extrahepatic tissues. Enzyme deficiency may be due to a variety of human mutations and can be fatal. Diminished activity has been explained based on analyses of recombinant human mutant proteins or, more recently, in the context of structural models for the enzyme. We report the experimental determination of a crystal structure at 2.1 A resolution of the recombinant human mitochondrial HMG-CoA lyase containing a bound activator cation and the dicarboxylic acid 3-hydroxyglutarate. The enzyme adopts a (betaalpha)(8) barrel fold, and the N-terminal barrel end is occluded. The structure of a physiologically relevant dimer suggests that substrate access to the active site involves binding across the cavity located at the C-terminal end of the barrel. An alternative hypothesis that involves substrate insertion through a pore proposed to extend through the barrel is not compatible with the observed structure. The activator cation ligands included Asn(275), Asp(42),His(233), and His(235); the latter three residues had been implicated previously as contributing to metal binding or enzyme activity. Arg(41), previously shown to have a major effect on catalytic efficiency, is also located at the active site. In the observed structure, this residue interacts with a carboxyl group of 3-hydroxyglutarate, the hydrolysis product of the competitive inhibitor 3-hydroxyglutaryl-CoA required for crystallization of human enzyme. The structure provides a rationale for the decrease in enzyme activity due to clinical mutations, including H233R, R41Q, D42H, and D204N, that compromise active site function or enzyme stability.
-
-	Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria.,Fu Z, Runquist JA, Forouhar F, Hussain M, Hunt JF, Miziorko HM, Kim JJ J Biol Chem. 2006 Mar 17;281(11):7526-32. Epub 2005 Dec 5. PMID:16330550<ref>PMID:16330550</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2cw6" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Hydroxymethylglutaryl-CoA lyase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fu, Z]]	+	[[Category: Fu Z]]
-	[[Category: Hunt~~, J F~~]]	+	[[Category: Hunt JF]]
-	[[Category: Kim, J ~~J.P~~]]	+	[[Category: Kim J-JP]]
-	[[Category: Miziorko~~, H M~~]]	+	[[Category: Miziorko HM]]
-	[[Category: Runquist~~, J A]]~~	+	[[Category: Runquist JA]]
-	~~[[Category: Hmg-coa lyase]]~~	+
-	~~[[Category: Ketogenic enzyme]]~~	+
-	~~[[Category: Lyase~~]]	+

OCA at 07:01, 1 December 2021

OCA — Wed, 01 Dec 2021 07:01:54 GMT

OCA at 11:01, 26 February 2020

OCA — Wed, 26 Feb 2020 11:01:38 GMT

←Older revision		Revision as of 11:01, 26 February 2020
Line 1:		Line 1:

	==Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria==		==Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria==
-	<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='2cw6' size='340' side='right'caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
Line 37:		Line 37:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]
		+	[[Category: Large Structures]]
	[[Category: Fu, Z]]		[[Category: Fu, Z]]
	[[Category: Hunt, J F]]		[[Category: Hunt, J F]]

OCA at 08:27, 23 May 2018

OCA — Wed, 23 May 2018 08:27:06 GMT

←Older revision		Revision as of 08:27, 23 May 2018
Line 1:		Line 1:
		+
	==Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria==		==Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria==
	<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://pdbe.org/2cw6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://pdbe.org/2cw6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2cw6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cw/2cw6_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cw/2cw6_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cw6 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:51, 11 September 2015

OCA — Fri, 11 Sep 2015 07:51:37 GMT

←Older revision		Revision as of 07:51, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://pdbe.org/2cw6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2cw6" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]
	[[Category: Fu, Z]]		[[Category: Fu, Z]]

OCA at 16:46, 15 January 2015

OCA — Thu, 15 Jan 2015 16:46:16 GMT

←Older revision		Revision as of 16:46, 15 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[http://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>		[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[http://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>
Line 35:		Line 35:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]
-	[[Category: Fu, Z.]]	+	[[Category: Fu, Z]]
-	[[Category: Hunt, J F.]]	+	[[Category: Hunt, J F]]
-	[[Category: Kim, J J.P.]]	+	[[Category: Kim, J J.P]]
-	[[Category: Miziorko, H M.]]	+	[[Category: Miziorko, H M]]
-	[[Category: Runquist, J A.]]	+	[[Category: Runquist, J A]]
	[[Category: Hmg-coa lyase]]		[[Category: Hmg-coa lyase]]
	[[Category: Ketogenic enzyme]]		[[Category: Ketogenic enzyme]]
	[[Category: Lyase]]		[[Category: Lyase]]

OCA at 00:15, 30 September 2014

OCA — Tue, 30 Sep 2014 00:15:49 GMT

←Older revision		Revision as of 00:15, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2cw6\| PDB=2cw6 \| SCENE= }}~~	+	==Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria==
-	===Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria===	+	<StructureSection load='2cw6' size='340' side='right' caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
-	~~{{ABSTRACT_PUBMED_16330550}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [http://www.ebi.ac.uk/pdbsum/2cw6 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[http://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref> <ref>PMID:22865860</ref> <ref>PMID:22847177</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cw/2cw6_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase is a key enzyme in the ketogenic pathway that supplies metabolic fuel to extrahepatic tissues. Enzyme deficiency may be due to a variety of human mutations and can be fatal. Diminished activity has been explained based on analyses of recombinant human mutant proteins or, more recently, in the context of structural models for the enzyme. We report the experimental determination of a crystal structure at 2.1 A resolution of the recombinant human mitochondrial HMG-CoA lyase containing a bound activator cation and the dicarboxylic acid 3-hydroxyglutarate. The enzyme adopts a (betaalpha)(8) barrel fold, and the N-terminal barrel end is occluded. The structure of a physiologically relevant dimer suggests that substrate access to the active site involves binding across the cavity located at the C-terminal end of the barrel. An alternative hypothesis that involves substrate insertion through a pore proposed to extend through the barrel is not compatible with the observed structure. The activator cation ligands included Asn(275), Asp(42),His(233), and His(235); the latter three residues had been implicated previously as contributing to metal binding or enzyme activity. Arg(41), previously shown to have a major effect on catalytic efficiency, is also located at the active site. In the observed structure, this residue interacts with a carboxyl group of 3-hydroxyglutarate, the hydrolysis product of the competitive inhibitor 3-hydroxyglutaryl-CoA required for crystallization of human enzyme. The structure provides a rationale for the decrease in enzyme activity due to clinical mutations, including H233R, R41Q, D42H, and D204N, that compromise active site function or enzyme stability.

-	~~==Disease==~~	+	Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria.,Fu Z, Runquist JA, Forouhar F, Hussain M, Hunt JF, Miziorko HM, Kim JJ J Biol Chem. 2006 Mar 17;281(11):7526-32. Epub 2005 Dec 5. PMID:16330550<ref>PMID:16330550</ref>
-	~~[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause~~ of 3-hydroxy-3-methylglutaryl-CoA ~~lyase deficiency (HMGCLD) [MIM~~:~~[http://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis~~ and ~~L-leucine catabolism~~. ~~The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting~~, ~~seizures~~, ~~metabolic acidosis~~, ~~hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma~~, ~~with fatal outcome in some cases~~.~~<ref>PMID~~:~~8798725</ref><ref>~~PMID:~~9463337</ref><ref>PMID:9784232</ref><ref>PMID:11129331</ref><ref>PMID:12746442</ref><ref>PMID:17173698</ref><ref>PMID:16601870</ref><ref>PMID:17459752</ref><ref>PMID:19036343</ref>~~<ref>PMID:~~19177531~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www~~.~~uniprot~~.~~org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism~~.<~~ref~~>~~PMID:8566388~~</~~ref><ref>PMID:22865860</ref><ref>PMID:22847177</ref~~>	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:016330550</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]

OCA at 03:45, 25 March 2013

OCA — Mon, 25 Mar 2013 03:45:20 GMT

←Older revision		Revision as of 03:45, 25 March 2013
Line 1:		Line 1:
-	[[Image:2cw6.png\|left\|200px]]
-
	{{STRUCTURE_2cw6\| PDB=2cw6 \| SCENE= }}		{{STRUCTURE_2cw6\| PDB=2cw6 \| SCENE= }}
-
	===Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria===		===Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria===
		+	{{ABSTRACT_PUBMED_16330550}}

-	~~{{ABSTRACT_PUBMED_16330550}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[http://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref><ref>PMID:9463337</ref><ref>PMID:9784232</ref><ref>PMID:11129331</ref><ref>PMID:12746442</ref><ref>PMID:17173698</ref><ref>PMID:16601870</ref><ref>PMID:17459752</ref><ref>PMID:19036343</ref><ref>PMID:19177531</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref><ref>PMID:22865860</ref><ref>PMID:22847177</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:016330550</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016330550</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]

OCA: Protected "2cw6" [edit=sysop:move=sysop]

OCA — Sun, 06 Jan 2013 09:40:25 GMT

Protected "2cw6" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:40, 6 January 2013

OCA at 09:40, 6 January 2013

OCA — Sun, 06 Jan 2013 09:40:24 GMT

←Older revision		Revision as of 09:40, 6 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2cw6.png\|left\|200px]]		[[Image:2cw6.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2cw6", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2cw6\| PDB=2cw6 \| SCENE= }}		{{STRUCTURE_2cw6\| PDB=2cw6 \| SCENE= }}

	===Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria===		===Crystal Structure of Human HMG-CoA Lyase: Insights into Catalysis and the Molecular Basis for Hydroxymethylglutaric Aciduria===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_16330550}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 16330550 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_16330550}}		{{ABSTRACT_PUBMED_16330550}}

	==About this Structure==		==About this Structure==
-	~~2CW6~~ is a 6 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA].	+	[[2cw6]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~16330550~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016330550</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Hydroxymethylglutaryl-CoA lyase]]		[[Category: Hydroxymethylglutaryl-CoA lyase]]
Line 33:		Line 21:
	[[Category: Hmg-coa lyase]]		[[Category: Hmg-coa lyase]]
	[[Category: Ketogenic enzyme]]		[[Category: Ketogenic enzyme]]
-		+	[[Category: Lyase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Tue Feb 17 17:26:09 2009''~~	+

←Older revision		Revision as of 07:01, 1 December 2021
Line 3:		Line 3:
	<StructureSection load='2cw6' size='340' side='right'caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='2cw6' size='340' side='right'caption='[[2cw6]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2cw6]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CW6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3HG:3-HYDROXYPENTANEDIOIC+ACID'>3HG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_lyase Hydroxymethylglutaryl-CoA lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.4 4.1.3.4] </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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [~~http~~://pdbe.org/2cw6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2cw6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2cw6 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=2cw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cw6 OCA], [https://pdbe.org/2cw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cw6 RCSB], [https://www.ebi.ac.uk/pdbsum/2cw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cw6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[~~http~~://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>	+	[[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Defects in HMGCL are the cause of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) [MIM:[https://omim.org/entry/246450 246450]]; also known as hydroxymethylglutaricaciduria or HL deficiency. An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.<ref>PMID:8798725</ref> <ref>PMID:9463337</ref> <ref>PMID:9784232</ref> <ref>PMID:11129331</ref> <ref>PMID:12746442</ref> <ref>PMID:17173698</ref> <ref>PMID:16601870</ref> <ref>PMID:17459752</ref> <ref>PMID:19036343</ref> <ref>PMID:19177531</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref> <ref>PMID:22865860</ref> <ref>PMID:22847177</ref>	+	[[https://www.uniprot.org/uniprot/HMGCL_HUMAN HMGCL_HUMAN]] Key enzyme in ketogenesis (ketone body formation). Terminal step in leucine catabolism.<ref>PMID:8566388</ref> <ref>PMID:22865860</ref> <ref>PMID:22847177</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]