4eak - Revision history

OCA at 13:46, 8 November 2023

2023-11-08T13:46:51Z

← Older revision		Revision as of 13:46, 8 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EAK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EAK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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]] 2.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [https://pdbe.org/4eak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [https://www.ebi.ac.uk/pdbsum/4eak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak 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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [https://pdbe.org/4eak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [https://www.ebi.ac.uk/pdbsum/4eak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref>		[https://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:00, 28 September 2022

2022-09-28T07:00:39Z

← Older revision		Revision as of 07:00, 28 September 2022
Line 3:		Line 3:
	<StructureSection load='4eak' size='340' side='right'caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4eak' size='340' side='right'caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EAK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EAK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]~~</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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [https://pdbe.org/4eak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [https://www.ebi.ac.uk/pdbsum/4eak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak 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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [~~http~~://pdbe.org/4eak PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eak PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref> [[http://www.uniprot.org/uniprot/AAKG1_RAT AAKG1_RAT]] 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:17851531</ref> <ref>PMID:21399626</ref> [[http://www.uniprot.org/uniprot/AAKB1_RAT AAKB1_RAT]] 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/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chen, L]]		[[Category: Rattus norvegicus]]
	[[Category: Neumann, D]]		[[Category: Chen L]]
	[[Category: Schlattner, U]]		[[Category: Neumann D]]
	[[Category: Wang, J]]		[[Category: Schlattner U]]
	[[Category: Wang, Z X]]		[[Category: Wang J]]
	[[Category: Wu, J W]]		[[Category: Wang Z-X]]
	[[Category: Yan~~, S F~~]]		[[Category: Wu J-W]]
	[[Category: Zhang, Y Y]]		[[Category: Yan SF]]
	~~[[Category: Ampk]]~~		[[Category: Zhang Y-Y]]
	~~[[Category: Transferase~~]]

OCA at 09:33, 5 February 2020

2020-02-05T09:33:25Z

← Older revision		Revision as of 09:33, 5 February 2020
Line 1:		Line 1:

	==Co-crystal structure of an AMPK core with ATP==		==Co-crystal structure of an AMPK core with ATP==
	<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4eak' size='340' side='right'caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EAK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EAK FirstGlance]. <br>
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4eak" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eak" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[AMP-activated protein kinase 3D structures\|AMP-activated protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Chen, L]]		[[Category: Chen, L]]
	[[Category: Neumann, D]]		[[Category: Neumann, D]]

OCA at 14:55, 15 November 2017

2017-11-15T14:55:51Z

← Older revision		Revision as of 14:55, 15 November 2017
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 4eak" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eak" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[AMP-activated protein kinase\|AMP-activated protein kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:43, 3 August 2017

2017-08-03T10:43:24Z

← Older revision		Revision as of 10:43, 3 August 2017
Line 3:		Line 3:
	<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure ~~with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]~~. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EAK FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EAK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaa1, Ampk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkab1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [http://pdbe.org/4eak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [http://www.ebi.ac.uk/pdbsum/4eak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak 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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [http://pdbe.org/4eak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [http://www.ebi.ac.uk/pdbsum/4eak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak ProSAT]</span></td></tr>
	</table>		</table>
Line 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Buffalo rat]]~~
	[[Category: Chen, L]]		[[Category: Chen, L]]
	[[Category: Neumann, D]]		[[Category: Neumann, D]]

OCA at 18:17, 4 August 2016

2016-08-04T18:17:30Z

← Older revision		Revision as of 18:17, 4 August 2016
Line 1:		Line 1:

	==Co-crystal structure of an AMPK core with ATP==		==Co-crystal structure of an AMPK core with ATP==
	<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaa1, Ampk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkab1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaa1, Ampk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkab1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [http://www.ebi.ac.uk/pdbsum/4eak 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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [http://pdbe.org/4eak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [http://www.ebi.ac.uk/pdbsum/4eak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eak ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4eak" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:49, 25 December 2014

2014-12-25T11:49:48Z

← Older revision		Revision as of 11:49, 25 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4eak~~\| ~~PDB~~=4eak \| ~~SCENE~~= }}		==Co-crystal structure of an AMPK core with ATP==
	===Co-~~crystal~~ structure of an AMPK ~~core with~~ ATP===		<StructureSection load='4eak' size='340' side='right' caption='[[4eak]], [[Resolution\|resolution]] 2.50Å' scene=''>
	~~{{ABSTRACT_PUBMED_22659875}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4eak]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EAK FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4eag\|4eag]], [[4eai\|4eai]], [[4eaj\|4eaj]], [[4eal\|4eal]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Prkaa1, Ampk1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkab1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Prkag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=4eak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eak OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eak RCSB], [http://www.ebi.ac.uk/pdbsum/4eak PDBsum]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref> [[http://www.uniprot.org/uniprot/AAKG1_RAT AAKG1_RAT]] 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:17851531</ref> <ref>PMID:21399626</ref> [[http://www.uniprot.org/uniprot/AAKB1_RAT AAKB1_RAT]] 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 energy sensor AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is allosterically activated by AMP binding to the gamma subunit. Cocrystal structures of the mammalian AMPK core reveal occlusion of nucleotide-binding site 3 of the gamma subunit in the presence of ATP. However, site 3 is occupied in the presence of AMP. Mutagenesis studies indicate that sites 3 and 4 are important for AMPK allosteric activation.

	~~==Function==~~		AMP-activated protein kinase undergoes nucleotide-dependent conformational changes.,Chen L, Wang J, Zhang YY, Yan SF, Neumann D, Schlattner U, Wang ZX, Wu JW Nat Struct Mol Biol. 2012 Jun 3;19(7):716-8. doi: 10.1038/nsmb.2319. PMID:22659875<ref>PMID:22659875</ref>
	~~[[http://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:~~21204788</ref> [[http://www.uniprot~~.~~org~~/uniprot/AAKG1_RAT AAKG1_RAT]] 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:~~17851531</ref>~~ <ref>PMID:~~21399626~~</ref> [[http://www.uniprot.org/uniprot/AAKB1_RAT AAKB1_RAT]] 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).

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4eak]] is~~ a ~~3 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Buffalo_rat Buffalo rat]~~. ~~Full crystallographic information is available from [http:/~~/~~oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA].~~		</div>

	==See Also==		==See Also==
	*[[AMP-activated protein kinase\|AMP-activated protein kinase]]		*[[AMP-activated protein kinase\|AMP-activated protein kinase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:022659875</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Buffalo rat]]		[[Category: Buffalo rat]]
	[[Category: Chen, L.]]		[[Category: Chen, L]]
	[[Category: Neumann, D.]]		[[Category: Neumann, D]]
	[[Category: Schlattner, U.]]		[[Category: Schlattner, U]]
	[[Category: Wang, J.]]		[[Category: Wang, J]]
	[[Category: Wang, Z X.]]		[[Category: Wang, Z X]]
	[[Category: Wu, J W.]]		[[Category: Wu, J W]]
	[[Category: Yan, S F.]]		[[Category: Yan, S F]]
	[[Category: Zhang, Y Y.]]		[[Category: Zhang, Y Y]]
	[[Category: Ampk]]		[[Category: Ampk]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 13:39, 12 March 2014

2014-03-12T13:39:20Z

← Older revision		Revision as of 13:39, 12 March 2014
Line 1:		Line 1:
	~~[[Image:4eak.jpg\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4eak", 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_4eak\| PDB=4eak \| SCENE= }}		{{STRUCTURE_4eak\| PDB=4eak \| SCENE= }}

	===Co-crystal structure of an AMPK core with ATP===		===Co-crystal structure of an AMPK core with ATP===
			{{ABSTRACT_PUBMED_22659875}}

			==Function==
			[[http://www.uniprot.org/uniprot/AAPK1_RAT AAPK1_RAT]] 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.<ref>PMID:2369897</ref> <ref>PMID:9029219</ref> <ref>PMID:10025949</ref> <ref>PMID:11069105</ref> <ref>PMID:11598104</ref> <ref>PMID:11724780</ref> <ref>PMID:12065600</ref> <ref>PMID:14511394</ref> <ref>PMID:12740371</ref> <ref>PMID:14709557</ref> <ref>PMID:17341212</ref> <ref>PMID:21204788</ref> [[http://www.uniprot.org/uniprot/AAKG1_RAT AAKG1_RAT]] 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:17851531</ref> <ref>PMID:21399626</ref> [[http://www.uniprot.org/uniprot/AAKB1_RAT AAKB1_RAT]] 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).

	==About this Structure==		==About this Structure==
	[[4eak]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus,_synthetic,_rattus_norvegicus Rattus norvegicus, synthetic, rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA].		[[4eak]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EAK OCA].
	[[~~Category: Rattus norvegicus~~]]
	[[Category: ~~Rattus norvegicus, synthetic, rattus norvegicus~~]]		==See Also==
			*[[AMP-activated protein kinase\|AMP-activated protein kinase]]

			==Reference==
			<ref group="xtra">PMID:022659875</ref><references group="xtra"/><references/>
			[[Category: Buffalo rat]]
	[[Category: Chen, L.]]		[[Category: Chen, L.]]
	[[Category: Neumann, D.]]		[[Category: Neumann, D.]]

OCA at 07:55, 6 June 2012

2012-06-06T07:55:37Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4eak.jpg|left|200px]]
-The entry 4eak is ON HOLD  until Paper Publication
+<!--
-Authors: Chen, L., Wang, J., Zhang, Y.-Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.-X., Wu, J.-W.
+===Co-crystal structure of an AMPK core with ATP===
-Description: Co-crystal structure of an AMPK core with ATP

OCA at 07:30, 18 April 2012

2012-04-18T07:30:07Z

← Older revision		Revision as of 07:30, 18 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4eak is ON HOLD		The entry 4eak is ON HOLD until Paper Publication

	Authors: Chen, L., Wang, J., Zhang, Y.-Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.-X., Wu, J.-W.		Authors: Chen, L., Wang, J., Zhang, Y.-Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.-X., Wu, J.-W.

	Description: Co-crystal structure of an AMPK core with ATP		Description: Co-crystal structure of an AMPK core with ATP