6b1u - Revision history

OCA at 14:30, 4 October 2023

OCA — Wed, 04 Oct 2023 14:30:37 GMT

←Older revision		Revision as of 14:30, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6b1u' size='340' side='right'caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>		<StructureSection load='6b1u' size='340' side='right'caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6b1u]] 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=6B1U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6B1U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6b1u]] 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=6B1U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B1U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CG7:5-{[6-chloro-5-(2-hydroxy[1,1-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic+acid'>CG7</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=~~STU~~:~~STAUROSPORINE~~'>~~STU~~</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]] 2.77Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=~~SEP~~:~~PHOSPHOSERINE~~'>~~SEP~~</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CG7:5-{[6-chloro-5-(2-hydroxy[1,1-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic+acid'>CG7</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKAA2, AMPK, AMPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRKAB1, AMPK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRKAG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6b1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1u OCA], [https://pdbe.org/6b1u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b1u RCSB], [https://www.ebi.ac.uk/pdbsum/6b1u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1u ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6b1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1u OCA], [~~http~~://pdbe.org/6b1u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6b1u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6b1u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1u ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB1_HUMAN AAKB1_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).	+	[https://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Baell~~, J B~~]]	+	[[Category: Baell JB]]
-	[[Category: Bozikis~~, Y E~~]]	+	[[Category: Bozikis YE]]
-	[[Category: Camerino~~, M C~~]]	+	[[Category: Camerino MC]]
-	[[Category: Dite~~, T A~~]]	+	[[Category: Dite TA]]
-	[[Category: Foitzik~~, R C~~]]	+	[[Category: Foitzik RC]]
-	[[Category: Hoque, A]]	+	[[Category: Hoque A]]
-	[[Category: Huang, H]]	+	[[Category: Huang H]]
-	[[Category: Jacobs, R]]	+	[[Category: Jacobs R]]
-	[[Category: Johnson, S]]	+	[[Category: Johnson S]]
-	[[Category: Kemp~~, B E~~]]	+	[[Category: Kemp BE]]
-	[[Category: Langendorf~~, C G~~]]	+	[[Category: Langendorf CG]]
-	[[Category: Ling~~, N X.Y~~]]	+	[[Category: Ling NXY]]
-	[[Category: Ngoei~~, K R.W~~]]	+	[[Category: Ngoei KRW]]
-	[[Category: Oakhill~~, J S~~]]	+	[[Category: Oakhill JS]]
-	[[Category: Ovens~~, A J~~]]	+	[[Category: Ovens AJ]]
-	[[Category: Parker~~, M W~~]]	+	[[Category: Parker MW]]
-	[[Category: Rider~~, M H~~]]	+	[[Category: Rider MH]]
-	[[Category: Scott~~, J W~~]]	+	[[Category: Scott JW]]
-	[[Category: Smiles~~, W J~~]]	+	[[Category: Smiles WJ]]
-	[[Category: Walker~~, S R]]~~	+	[[Category: Walker SR]]
-	~~[[Category: Active]]~~	+
-	~~[[Category: Heterotrimer]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Phosphorylated]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 10:11, 1 January 2020

OCA — Wed, 01 Jan 2020 10:11:30 GMT

←Older revision		Revision as of 10:11, 1 January 2020
Line 1:		Line 1:

	==Structure of full-length human AMPK (a2b1g1) in complex with a small molecule activator SC4==		==Structure of full-length human AMPK (a2b1g1) in complex with a small molecule activator SC4==
-	<StructureSection load='6b1u' size='340' side='right' caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>	+	<StructureSection load='6b1u' size='340' side='right'caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6b1u]] 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=6B1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1U FirstGlance]. <br>		<table><tr><td colspan='2'>[[6b1u]] 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=6B1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1U FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6b1u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6b1u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[AMP-activated protein kinase 3D structures\|AMP-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Baell, J B]]		[[Category: Baell, J B]]
	[[Category: Bozikis, Y E]]		[[Category: Bozikis, Y E]]

OCA at 08:30, 2 May 2018

OCA — Wed, 02 May 2018 08:30:15 GMT

←Older revision		Revision as of 08:30, 2 May 2018
Line 3:		Line 3:
	<StructureSection load='6b1u' size='340' side='right' caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>		<StructureSection load='6b1u' size='340' side='right' caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6b1u]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6b1u]] 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=6B1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1U FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CG7:5-{[6-chloro-5-(2-hydroxy[1,1-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic+acid'>CG7</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CG7:5-{[6-chloro-5-(2-hydroxy[1,1-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic+acid'>CG7</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PRKAA2, AMPK, AMPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRKAB1, AMPK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRKAG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6b1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1u OCA], [http://pdbe.org/6b1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1u RCSB], [http://www.ebi.ac.uk/pdbsum/6b1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1u ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1u OCA], [http://pdbe.org/6b1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1u RCSB], [http://www.ebi.ac.uk/pdbsum/6b1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1u ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB1_HUMAN AAKB1_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).		[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB1_HUMAN AAKB1_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The AMP-activated protein kinase (AMPK) alphabetagamma heterotrimer regulates cellular energy homeostasis with tissue-specific isoform distribution. Small-molecule activation of skeletal muscle alpha2beta2 AMPK complexes may prove a valuable treatment strategy for type 2 diabetes and insulin resistance. Herein, we report the small-molecule SC4 is a potent, direct AMPK activator that preferentially activates alpha2 complexes and stimulates skeletal muscle glucose uptake. In parallel with the term secretagog, we propose "importagog" to define a substance that induces or augments cellular uptake of another substance. Three-dimensional structures of the glucose importagog SC4 bound to activated alpha2beta2gamma1 and alpha2beta1gamma1 complexes reveal binding determinants, in particular a key interaction between the SC4 imidazopyridine 4'-nitrogen and beta2-Asp111, which provide a design paradigm for beta2-AMPK therapeutics. The alpha2beta2gamma1/SC4 structure reveals an interaction between a beta2 N-terminal alpha helix and the alpha2 autoinhibitory domain. Our results provide a structure-function guide to accelerate development of potent, but importantly tissue-specific, beta2-AMPK therapeutics.
		+
		+	Structural Determinants for Small-Molecule Activation of Skeletal Muscle AMPK alpha2beta2gamma1 by the Glucose Importagog SC4.,Ngoei KRW, Langendorf CG, Ling NXY, Hoque A, Varghese S, Camerino MA, Walker SR, Bozikis YE, Dite TA, Ovens AJ, Smiles WJ, Jacobs R, Huang H, Parker MW, Scott JW, Rider MH, Foitzik RC, Kemp BE, Baell JB, Oakhill JS Cell Chem Biol. 2018 Apr 12. pii: S2451-9456(18)30110-7. doi:, 10.1016/j.chembiol.2018.03.008. PMID:29657085<ref>PMID:29657085</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6b1u" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Baell, J B]]		[[Category: Baell, J B]]
	[[Category: Bozikis, Y E]]		[[Category: Bozikis, Y E]]

OCA at 05:32, 25 April 2018

OCA — Wed, 25 Apr 2018 05:32:51 GMT

←Older revision		Revision as of 05:32, 25 April 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6b1u is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Structure of full-length human AMPK (a2b1g1) in complex with a small molecule activator SC4==
-		+	<StructureSection load='6b1u' size='340' side='right' caption='[[6b1u]], [[Resolution\|resolution]] 2.77Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6b1u]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B1U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1U FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CG7:5-{[6-chloro-5-(2-hydroxy[1,1-biphenyl]-4-yl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy}-2-methylbenzoic+acid'>CG7</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6b1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1u OCA], [http://pdbe.org/6b1u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1u RCSB], [http://www.ebi.ac.uk/pdbsum/6b1u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1u ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref> [[http://www.uniprot.org/uniprot/AAKG1_HUMAN AAKG1_HUMAN]] AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.<ref>PMID:21680840</ref> [[http://www.uniprot.org/uniprot/AAKB1_HUMAN AAKB1_HUMAN]] Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Baell, J B]]
		+	[[Category: Bozikis, Y E]]
		+	[[Category: Camerino, M C]]
		+	[[Category: Dite, T A]]
		+	[[Category: Foitzik, R C]]
		+	[[Category: Hoque, A]]
		+	[[Category: Huang, H]]
		+	[[Category: Jacobs, R]]
		+	[[Category: Johnson, S]]
		+	[[Category: Kemp, B E]]
		+	[[Category: Langendorf, C G]]
		+	[[Category: Ling, N X.Y]]
		+	[[Category: Ngoei, K R.W]]
		+	[[Category: Oakhill, J S]]
		+	[[Category: Ovens, A J]]
		+	[[Category: Parker, M W]]
		+	[[Category: Rider, M H]]
		+	[[Category: Scott, J W]]
		+	[[Category: Smiles, W J]]
		+	[[Category: Walker, S R]]
		+	[[Category: Active]]
		+	[[Category: Heterotrimer]]
		+	[[Category: Kinase]]
		+	[[Category: Phosphorylated]]
		+	[[Category: Transferase]]

OCA at 06:02, 6 December 2017

OCA — Wed, 06 Dec 2017 06:02:36 GMT

←Older revision		Revision as of 06:02, 6 December 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6b1u is ON HOLD	+	The entry 6b1u is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6b1u" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 17:04:27 GMT

Protected "6b1u" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:04, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6b1u is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 17:04:26 GMT

New page: '''Unreleased structure''' The entry 6b1u is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6b1u is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]