2q8i - Revision history

OCA at 11:25, 30 August 2023

OCA — Wed, 30 Aug 2023 11:25:10 GMT

←Older revision		Revision as of 11:25, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='2q8i' size='340' side='right'caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2q8i' size='340' side='right'caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~, ~~<scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</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]] 2.6Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td><~~td class~~=~~"sblockDat">PDK3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([https~~:~~//www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td~~></tr>	+
-	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>[https://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </~~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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [https://pdbe.org/2q8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [https://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i 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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [https://pdbe.org/2q8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [https://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[https://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref> [[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.	+	[https://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 40:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chuang~~, D T~~]]	+	[[Category: Chuang DT]]
-	[[Category: Chuang~~, J L~~]]	+	[[Category: Chuang JL]]
-	[[Category: Kato, M]]	+	[[Category: Kato M]]
-	[[Category: Li, J]]	+	[[Category: Li J]]
-	~~[[Category: Ghkl atpase/kinase family]]~~	+
-	~~[[Category: Mitochondrial kinase]]~~	+
-	~~[[Category: Pyruvate dehydrogenase complex]]~~	+
-	~~[[Category: Radicicol]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:12, 25 June 2021

OCA — Fri, 25 Jun 2021 08:12:06 GMT

←Older revision		Revision as of 08:12, 25 June 2021
Line 1:		Line 1:

	==Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol==		==Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol==
-	<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='2q8i' size='340' side='right'caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [~~http~~://pdbe.org/2q8i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i 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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [https://pdbe.org/2q8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [https://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[~~http~~://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.	+	[[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[https://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref> [[~~http~~://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.	+	[[https://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref> [[https://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q8/2q8i_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q8/2q8i_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>
Line 41:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chuang, D T]]		[[Category: Chuang, D T]]
	[[Category: Chuang, J L]]		[[Category: Chuang, J L]]

OCA at 09:41, 18 October 2017

OCA — Wed, 18 Oct 2017 09:41:18 GMT

←Older revision		Revision as of 09:41, 18 October 2017
Line 1:		Line 1:
		+
	==Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol==		==Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol==
	<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://pdbe.org/2q8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i 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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://pdbe.org/2q8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	<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=2q8i ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 08:34, 11 September 2015

OCA — Fri, 11 Sep 2015 08:34:26 GMT

←Older revision		Revision as of 08:34, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i 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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://pdbe.org/2q8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 31:
	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 2q8i" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Chuang, D T]]		[[Category: Chuang, D T]]
	[[Category: Chuang, J L]]		[[Category: Chuang, J L]]

OCA at 15:37, 19 January 2015

OCA — Mon, 19 Jan 2015 15:37:59 GMT

←Older revision		Revision as of 15:37, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>		<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i 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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[http://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.		[[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[http://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Chuang, D T.]]	+	[[Category: Chuang, D T]]
-	[[Category: Chuang, J L.]]	+	[[Category: Chuang, J L]]
-	[[Category: Kato, M.]]	+	[[Category: Kato, M]]
-	[[Category: Li, J.]]	+	[[Category: Li, J]]
	[[Category: Ghkl atpase/kinase family]]		[[Category: Ghkl atpase/kinase family]]
	[[Category: Mitochondrial kinase]]		[[Category: Mitochondrial kinase]]

OCA at 18:51, 30 September 2014

OCA — Tue, 30 Sep 2014 18:51:14 GMT

←Older revision		Revision as of 18:51, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2q8i\| PDB=2q8i \| SCENE= }}~~	+	==Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol==
-	===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===	+	<StructureSection load='2q8i' size='340' side='right' caption='[[2q8i]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_17683942}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[2q8i]] is a 2 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=2Q8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q8I FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene>, <scene name='pdbligand=RED:DIHYDROLIPOIC+ACID'>RED</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2q8f\|2q8f]], [[2q8g\|2q8g]], [[2q8h\|2q8h]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PDK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DLAT, DLTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] </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=2q8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q8i RCSB], [http://www.ebi.ac.uk/pdbsum/2q8i PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[http://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.		[[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[http://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref> <ref>PMID:11486000</ref> <ref>PMID:16436377</ref> <ref>PMID:18718909</ref> <ref>PMID:22865452</ref> <ref>PMID:15861126</ref> <ref>PMID:17683942</ref> [[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
		+	== 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/q8/2q8i_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 ==
		+	Pyruvate dehydrogenase kinase (PDK) isoforms are molecular switches that downregulate the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation in mitochondria. We have determined structures of human PDK1 or PDK3 bound to the inhibitors AZD7545, dichloroacetate (DCA), and radicicol. We show that the trifluoromethylpropanamide end of AZD7545 projects into the lipoyl-binding pocket of PDK1. This interaction results in inhibition of PDK1 and PDK3 activities by aborting kinase binding to the PDC scaffold. Paradoxically, AZD7545 at saturating concentrations robustly increases scaffold-free PDK3 activity, similar to the inner lipoyl domain. Good DCA density is present in the helix bundle in the N-terminal domain of PDK1. Bound DCA promotes local conformational changes that are communicated to both nucleotide-binding and lipoyl-binding pockets of PDK1, leading to the inactivation of kinase activity. Finally, radicicol inhibits kinase activity by binding directly to the ATP-binding pocket of PDK3, similar to Hsp90 and Topo VI from the same ATPase/kinase superfamily.

-	~~==Function==~~	+	Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol.,Kato M, Li J, Chuang JL, Chuang DT Structure. 2007 Aug;15(8):992-1004. Epub 2007 Aug 2. PMID:17683942<ref>PMID:17683942</ref>
-	~~[[http://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits~~ pyruvate dehydrogenase ~~activity~~ by ~~phosphorylation of the E1 subunit PDHA1~~, and ~~thereby regulates glucose metabolism and aerobic respiration~~. ~~Can also phosphorylate PDHA2~~. ~~Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high~~-~~fat diet~~. ~~Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation~~. ~~Plays a role in the generation of reactive oxygen species.<ref>~~PMID:~~10748134</ref><ref>PMID:11486000</ref><ref>PMID:16436377</ref><ref>PMID:18718909</ref><ref>PMID:22865452</ref><ref>PMID:15861126</ref>~~<ref>PMID:17683942</ref> [[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[2q8i]] is~~ a ~~2 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=2Q8I OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Pyruvate dehydrogenase kinase\|Pyruvate dehydrogenase kinase]]		*[[Pyruvate dehydrogenase kinase\|Pyruvate dehydrogenase kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017683942</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Chuang, D T.]]		[[Category: Chuang, D T.]]

OCA at 04:43, 25 March 2013

OCA — Mon, 25 Mar 2013 04:43:57 GMT

←Older revision		Revision as of 04:43, 25 March 2013
Line 2:		Line 2:
	===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===		===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===
	{{ABSTRACT_PUBMED_17683942}}		{{ABSTRACT_PUBMED_17683942}}
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] Note=Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex. Defects in DLAT are the cause of pyruvate dehydrogenase E2 deficiency (PDHE2 deficiency) [MIM:[http://omim.org/entry/245348 245348]]; also known as lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex. Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/PDK3_HUMAN PDK3_HUMAN]] Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.<ref>PMID:10748134</ref><ref>PMID:11486000</ref><ref>PMID:16436377</ref><ref>PMID:18718909</ref><ref>PMID:22865452</ref><ref>PMID:15861126</ref><ref>PMID:17683942</ref> [[http://www.uniprot.org/uniprot/ODP2_HUMAN ODP2_HUMAN]] The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.

	==About this Structure==		==About this Structure==
Line 10:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017683942</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017683942</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Chuang, D T.]]		[[Category: Chuang, D T.]]

OCA at 09:56, 11 March 2013

OCA — Mon, 11 Mar 2013 09:56:34 GMT

←Older revision		Revision as of 09:56, 11 March 2013
Line 1:		Line 1:
-	[[Image:2q8i.png\|left\|200px]]
-
	{{STRUCTURE_2q8i\| PDB=2q8i \| SCENE= }}		{{STRUCTURE_2q8i\| PDB=2q8i \| SCENE= }}
-
	===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===		===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===
-
	{{ABSTRACT_PUBMED_17683942}}		{{ABSTRACT_PUBMED_17683942}}

OCA: Protected "2q8i" [edit=sysop:move=sysop]

OCA — Mon, 07 Jan 2013 21:31:22 GMT

Protected "2q8i" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:31, 7 January 2013

OCA at 21:31, 7 January 2013

OCA — Mon, 07 Jan 2013 21:31:19 GMT

←Older revision		Revision as of 21:31, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2q8i.png\|left\|200px]]		[[Image:2q8i.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2q8i", 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_2q8i\| PDB=2q8i \| SCENE= }}		{{STRUCTURE_2q8i\| PDB=2q8i \| SCENE= }}

	===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===		===Pyruvate dehydrogenase kinase isoform 3 in complex with antitumor drug radicicol===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_17683942}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 17683942 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_17683942}}		{{ABSTRACT_PUBMED_17683942}}

	==About this Structure==		==About this Structure==
-	~~2Q8I~~ is a 2 ~~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=2Q8I OCA].	+	[[2q8i]] is a 2 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=2Q8I OCA].
		+
		+	==See Also==
		+	*[[Pyruvate dehydrogenase kinase\|Pyruvate dehydrogenase kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~17683942~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017683942</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Chuang, D T.]]		[[Category: Chuang, D T.]]
Line 33:		Line 24:
	[[Category: Pyruvate dehydrogenase complex]]		[[Category: Pyruvate dehydrogenase complex]]
	[[Category: Radicicol]]		[[Category: Radicicol]]
-		+	[[Category: Transferase]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Tue Feb 17 18:01:01 2009''~~	+