5uuu: Difference between revisions

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 <StructureSection load='5uuu' size='340' side='right'caption='[[5uuu]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5uuu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UUU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UUU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5uuu]] 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=5UUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UUU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=QRW:3-({[4-METHYL-5-(PYRIDIN-4-YL)-4H-1,2,4-TRIAZOL-3-YL]METHYL}AMINO)-N-[2-(TRIFLUOROMETHYL)BENZYL]BENZAMIDE'>QRW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uvc|5uvc]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=QRW:3-({[4-METHYL-5-(PYRIDIN-4-YL)-4H-1,2,4-TRIAZOL-3-YL]METHYL}AMINO)-N-[2-(TRIFLUOROMETHYL)BENZYL]BENZAMIDE'>QRW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Beta-adrenergic-receptor]_kinase [Beta-adrenergic-receptor] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.15 2.7.11.15] </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=5uuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uuu OCA], [https://pdbe.org/5uuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uuu RCSB], [https://www.ebi.ac.uk/pdbsum/5uuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uuu ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5uuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uuu OCA], [http://pdbe.org/5uuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uuu RCSB], [http://www.ebi.ac.uk/pdbsum/5uuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uuu ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ARBK1_HUMAN ARBK1_HUMAN]] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.<ref>PMID:19306925</ref>
+[https://www.uniprot.org/uniprot/ARBK1_HUMAN ARBK1_HUMAN] Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner.<ref>PMID:19306925</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of beta-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates beta-adrenergic receptor (betaAR)-mediated cAMP accumulation and prevents internalization of betaARs in beta2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
-Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure.,Okawa T, Aramaki Y, Yamamoto M, Kobayashi T, Fukumoto S, Toyoda Y, Henta T, Hata A, Ikeda S, Kaneko M, Hoffman ID, Sang BC, Zou H, Kawamoto T J Med Chem. 2017 Aug 24;60(16):6942-6990. doi: 10.1021/acs.jmedchem.7b00443. Epub, 2017 Aug 3. PMID:28699740<ref>PMID:28699740</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5uuu" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 17: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Hoffman, I D]]
+[[Category: Hoffman ID]]
-[[Category: Lawson, J D]]
+[[Category: Lawson JD]]
-[[Category: Heart failure]]
-[[Category: Inhibitor]]
-[[Category: Kinase]]
-[[Category: Transferase-transferase inhibitor complex]]