3hdn - Revision history

OCA at 09:59, 21 February 2024

2024-02-21T09:59:24Z

←Older revision		Revision as of 09:59, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3hdn' size='340' side='right'caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3hdn' size='340' side='right'caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HDN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HDN FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GMG:[4~~-~~(5-NAPHTHALEN-2-YL-1H-PYRROLO[2~~,~~3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</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]] 3.1Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3hdm\|3hdm]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>SGK, SGK1 ([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/Non~~-~~specific_serine/threonine_protein_kinase Non~~-~~specific serine/threonine protein kinase], with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.7.11.1~~ 2~~.7.11.1~~] </~~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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [https://pdbe.org/3hdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [https://www.ebi.ac.uk/pdbsum/3hdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdn 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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [https://pdbe.org/3hdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [https://www.ebi.ac.uk/pdbsum/3hdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SGK1_HUMAN SGK1_HUMAN]] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.<ref>PMID:18753299</ref> <ref>PMID:11410590</ref> <ref>PMID:11154281</ref> <ref>PMID:11696533</ref> <ref>PMID:12590200</ref> <ref>PMID:12397388</ref> <ref>PMID:14623317</ref> <ref>PMID:12650886</ref> <ref>PMID:12761204</ref> <ref>PMID:12911626</ref> <ref>PMID:12634932</ref> <ref>PMID:15044175</ref> <ref>PMID:14706641</ref> <ref>PMID:15319523</ref> <ref>PMID:15234985</ref> <ref>PMID:15040001</ref> <ref>PMID:15496163</ref> <ref>PMID:15888551</ref> <ref>PMID:15845389</ref> <ref>PMID:15737648</ref> <ref>PMID:16036218</ref> <ref>PMID:15733869</ref> <ref>PMID:16443776</ref> <ref>PMID:16982696</ref> <ref>PMID:17382906</ref> <ref>PMID:18005662</ref> <ref>PMID:18304449</ref> <ref>PMID:19447520</ref> <ref>PMID:19756449</ref> <ref>PMID:20511718</ref> <ref>PMID:20730100</ref> <ref>PMID:21865597</ref>	+	[https://www.uniprot.org/uniprot/SGK1_HUMAN SGK1_HUMAN] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.<ref>PMID:18753299</ref> <ref>PMID:11410590</ref> <ref>PMID:11154281</ref> <ref>PMID:11696533</ref> <ref>PMID:12590200</ref> <ref>PMID:12397388</ref> <ref>PMID:14623317</ref> <ref>PMID:12650886</ref> <ref>PMID:12761204</ref> <ref>PMID:12911626</ref> <ref>PMID:12634932</ref> <ref>PMID:15044175</ref> <ref>PMID:14706641</ref> <ref>PMID:15319523</ref> <ref>PMID:15234985</ref> <ref>PMID:15040001</ref> <ref>PMID:15496163</ref> <ref>PMID:15888551</ref> <ref>PMID:15845389</ref> <ref>PMID:15737648</ref> <ref>PMID:16036218</ref> <ref>PMID:15733869</ref> <ref>PMID:16443776</ref> <ref>PMID:16982696</ref> <ref>PMID:17382906</ref> <ref>PMID:18005662</ref> <ref>PMID:18304449</ref> <ref>PMID:19447520</ref> <ref>PMID:19756449</ref> <ref>PMID:20511718</ref> <ref>PMID:20730100</ref> <ref>PMID:21865597</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</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=3hdn 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=3hdn ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing.
-
-	Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors.,Hammond M, Washburn DG, Hoang HT, Manns S, Frazee JS, Nakamura H, Patterson JR, Trizna W, Wu C, Azzarano LM, Nagilla R, Nord M, Trejo R, Head MS, Zhao B, Smallwood AM, Hightower K, Laping NJ, Schnackenberg CG, Thompson SK Bioorg Med Chem Lett. 2009 Aug 1;19(15):4441-5. Epub 2009 May 18. PMID:19497745<ref>PMID:19497745</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3hdn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Hammond M]]
-	[[Category: Hammond, M]]	+	[[Category: Zhao B]]
-	[[Category: Zhao, B]]	+
-	~~[[Category: Agc protein kinase]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Endoplasmic reticulum]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Serine/threonine-protein kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 11:58, 13 October 2021

2021-10-13T11:58:23Z

←Older revision		Revision as of 11:58, 13 October 2021
Line 1:		Line 1:

	==Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2==		==Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2==
-	<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='3hdn' size='340' side='right'caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3HDN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HDN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hdm\|3hdm]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3hdm\|3hdm]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SGK, SGK1 ([~~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">SGK, SGK1 ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [~~http~~://pdbe.org/3hdn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3hdn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdn 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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [https://pdbe.org/3hdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [https://www.ebi.ac.uk/pdbsum/3hdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/SGK1_HUMAN SGK1_HUMAN]] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.<ref>PMID:18753299</ref> <ref>PMID:11410590</ref> <ref>PMID:11154281</ref> <ref>PMID:11696533</ref> <ref>PMID:12590200</ref> <ref>PMID:12397388</ref> <ref>PMID:14623317</ref> <ref>PMID:12650886</ref> <ref>PMID:12761204</ref> <ref>PMID:12911626</ref> <ref>PMID:12634932</ref> <ref>PMID:15044175</ref> <ref>PMID:14706641</ref> <ref>PMID:15319523</ref> <ref>PMID:15234985</ref> <ref>PMID:15040001</ref> <ref>PMID:15496163</ref> <ref>PMID:15888551</ref> <ref>PMID:15845389</ref> <ref>PMID:15737648</ref> <ref>PMID:16036218</ref> <ref>PMID:15733869</ref> <ref>PMID:16443776</ref> <ref>PMID:16982696</ref> <ref>PMID:17382906</ref> <ref>PMID:18005662</ref> <ref>PMID:18304449</ref> <ref>PMID:19447520</ref> <ref>PMID:19756449</ref> <ref>PMID:20511718</ref> <ref>PMID:20730100</ref> <ref>PMID:21865597</ref>	+	[[https://www.uniprot.org/uniprot/SGK1_HUMAN SGK1_HUMAN]] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.<ref>PMID:18753299</ref> <ref>PMID:11410590</ref> <ref>PMID:11154281</ref> <ref>PMID:11696533</ref> <ref>PMID:12590200</ref> <ref>PMID:12397388</ref> <ref>PMID:14623317</ref> <ref>PMID:12650886</ref> <ref>PMID:12761204</ref> <ref>PMID:12911626</ref> <ref>PMID:12634932</ref> <ref>PMID:15044175</ref> <ref>PMID:14706641</ref> <ref>PMID:15319523</ref> <ref>PMID:15234985</ref> <ref>PMID:15040001</ref> <ref>PMID:15496163</ref> <ref>PMID:15888551</ref> <ref>PMID:15845389</ref> <ref>PMID:15737648</ref> <ref>PMID:16036218</ref> <ref>PMID:15733869</ref> <ref>PMID:16443776</ref> <ref>PMID:16982696</ref> <ref>PMID:17382906</ref> <ref>PMID:18005662</ref> <ref>PMID:18304449</ref> <ref>PMID:19447520</ref> <ref>PMID:19756449</ref> <ref>PMID:20511718</ref> <ref>PMID:20730100</ref> <ref>PMID:21865597</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 33:

	==See Also==		==See Also==
-	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]	+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Hammond, M]]		[[Category: Hammond, M]]

OCA at 08:24, 12 December 2018

2018-12-12T08:24:21Z

←Older revision		Revision as of 08:24, 12 December 2018
Line 1:		Line 1:
		+
	==Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2==		==Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2==
	<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SGK, SGK1 ([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">SGK, SGK1 ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://pdbe.org/3hdn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn 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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://pdbe.org/3hdn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hdn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/3hdn_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/3hdn_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>

OCA at 00:41, 10 February 2016

2016-02-10T00:41:37Z

←Older revision		Revision as of 00:41, 10 February 2016
Line 2:		Line 2:
	<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HDN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HDN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hdm\|3hdm]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hdm\|3hdm]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SGK, SGK1 ([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">SGK, SGK1 ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn 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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://pdbe.org/3hdn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<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=3hdn ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3hdn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Hammond, M]]		[[Category: Hammond, M]]

OCA at 10:35, 25 December 2014

2014-12-25T10:35:40Z

←Older revision		Revision as of 10:35, 25 December 2014
Line 9:		Line 9:
	<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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn 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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SGK1_HUMAN SGK1_HUMAN]] Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1.<ref>PMID:18753299</ref> <ref>PMID:11410590</ref> <ref>PMID:11154281</ref> <ref>PMID:11696533</ref> <ref>PMID:12590200</ref> <ref>PMID:12397388</ref> <ref>PMID:14623317</ref> <ref>PMID:12650886</ref> <ref>PMID:12761204</ref> <ref>PMID:12911626</ref> <ref>PMID:12634932</ref> <ref>PMID:15044175</ref> <ref>PMID:14706641</ref> <ref>PMID:15319523</ref> <ref>PMID:15234985</ref> <ref>PMID:15040001</ref> <ref>PMID:15496163</ref> <ref>PMID:15888551</ref> <ref>PMID:15845389</ref> <ref>PMID:15737648</ref> <ref>PMID:16036218</ref> <ref>PMID:15733869</ref> <ref>PMID:16443776</ref> <ref>PMID:16982696</ref> <ref>PMID:17382906</ref> <ref>PMID:18005662</ref> <ref>PMID:18304449</ref> <ref>PMID:19447520</ref> <ref>PMID:19756449</ref> <ref>PMID:20511718</ref> <ref>PMID:20730100</ref> <ref>PMID:21865597</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 09:40, 8 December 2014

2014-12-08T09:40:17Z

←Older revision		Revision as of 09:40, 8 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3hdn.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2==
		+	<StructureSection load='3hdn' size='340' side='right' caption='[[3hdn]], [[Resolution\|resolution]] 3.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3hdn]] is a 1 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=3HDN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HDN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GMG:[4-(5-NAPHTHALEN-2-YL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PHENYL]ACETIC+ACID'>GMG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3hdm\|3hdm]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SGK, SGK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3hdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hdn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hdn RCSB], [http://www.ebi.ac.uk/pdbsum/3hdn PDBsum]</span></td></tr>
		+	</table>
		+	== 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/hd/3hdn_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 ==
		+	The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing.

-	~~{{STRUCTURE_3hdn\| PDB=3hdn \| SCENE= }}~~	+	Design and synthesis of orally bioavailable serum and glucocorticoid-regulated kinase 1 (SGK1) inhibitors.,Hammond M, Washburn DG, Hoang HT, Manns S, Frazee JS, Nakamura H, Patterson JR, Trizna W, Wu C, Azzarano LM, Nagilla R, Nord M, Trejo R, Head MS, Zhao B, Smallwood AM, Hightower K, Laping NJ, Schnackenberg CG, Thompson SK Bioorg Med Chem Lett. 2009 Aug 1;19(15):4441-5. Epub 2009 May 18. PMID:19497745<ref>PMID:19497745</ref>

-	~~===Crystal structure~~ of ~~serum and glucocorticoid-regulated kinase 1 in complex with compound 2===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_19497745}}~~	+	==See Also==
-		+	*[[Serine/threonine protein kinase\|Serine/threonine protein kinase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~3hdn]] is a 1 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=3HDN OCA~~].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:019497745<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
-	[[Category: Hammond, M.]]	+	[[Category: Hammond, M]]
-	[[Category: Zhao, B.]]	+	[[Category: Zhao, B]]
	[[Category: Agc protein kinase]]		[[Category: Agc protein kinase]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]

OCA: Protected "3hdn" [edit=sysop:move=sysop]

2013-03-06T15:04:19Z

Protected "3hdn" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:04, 6 March 2013

OCA at 15:04, 6 March 2013

2013-03-06T15:04:14Z

←Older revision		Revision as of 15:04, 6 March 2013
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3hdn.png\|left\|200px]]
-	[[Image:3hdn.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3hdn", 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_3hdn\| PDB=3hdn \| SCENE= }}		{{STRUCTURE_3hdn\| PDB=3hdn \| SCENE= }}

	===Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2===		===Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19497745}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19497745 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19497745}}		{{ABSTRACT_PUBMED_19497745}}

	==About this Structure==		==About this Structure==
-	~~3HDN~~ is a 1 chain structure of 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=3HDN OCA].	+	[[3hdn]] is a 1 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=3HDN OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19497745~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019497745</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
Line 31:		Line 19:
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
-	[[Category: Cytoplasm]]
	[[Category: Endoplasmic reticulum]]		[[Category: Endoplasmic reticulum]]
	[[Category: Kinase]]		[[Category: Kinase]]
Line 38:		Line 25:
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
-	[[Category: Polymorphism]]
	[[Category: Serine/threonine-protein kinase]]		[[Category: Serine/threonine-protein kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]
-	[[Category: Ubl conjugation]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 1 09:17:12 2009''

OCA at 06:17, 1 July 2009

2009-07-01T06:17:14Z

←Older revision		Revision as of 06:17, 1 July 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3hdn.jpg\|left\|200px]]

-	The ~~entry 3hdn~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3hdn", 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_3hdn\| PDB=3hdn \| SCENE= }}

-	~~Authors: Zhao, B., Hammond, M.~~	+	===Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2===

-	Description: Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~May 20 16~~:39:49 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19497745}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19497745 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19497745}}
		+
		+	==About this Structure==
		+	3HDN is a 1 chain structure of 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=3HDN OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19497745</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Hammond, M.]]
		+	[[Category: Zhao, B.]]
		+	[[Category: Agc protein kinase]]
		+	[[Category: Apoptosis]]
		+	[[Category: Atp-binding]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Endoplasmic reticulum]]
		+	[[Category: Kinase]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Nucleus]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Polymorphism]]
		+	[[Category: Serine/threonine-protein kinase]]
		+	[[Category: Transferase]]
		+	[[Category: Ubl conjugation]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 1 09:17:12 2009''

OCA at 13:39, 20 May 2009

2009-05-20T13:39:49Z

←Older revision		Revision as of 13:39, 20 May 2009
Line 3:		Line 3:
	The entry 3hdn is ON HOLD		The entry 3hdn is ON HOLD

-	Authors: ~~Hammond, M., Washburn, D.G., Hoang, T.H., Manns, S., Frazee, J.S., Nakamura, H., Patterson, J.R., Trizna, W., Azzarano, C. L.M., Nagilla, R., Nord, M., Trejo, R., Head, M.S.,~~ Zhao, B., ~~Smallwood~~, A.M.~~, Hightower, K., Laping, N.J., Schnackenberg, C.G., Tho~~	+	Authors: Zhao, B., Hammond, M.

-	Description: ~~CRYSTAL STRUCTURE OF SERUM AND GLUCOCORTICOID~~-~~REGULATED KINASE~~ 1 ~~IN COMPLEX WITH COMPOUND~~ 2	+	Description: Crystal structure of serum and glucocorticoid-regulated kinase 1 in complex with compound 2

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May ~~13 09~~:38:46 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 20 16:39:49 2009''