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6cmj
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6cmj is ON HOLD Authors: Williams, S.P., Reid, R.A., Price, D.J., Drewry, D.H. Description: Human CAMKK2 with GSK650393 [[Category: Unreleased Stru...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Human CAMKK2 with GSK650393== | |
| + | <StructureSection load='6cmj' size='340' side='right' caption='[[6cmj]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6cmj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=F6J:2-(2-methylpropyl)-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic+acid'>F6J</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CAMKK2, CAMKKB, KIAA0787 ([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/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </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=6cmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cmj OCA], [http://pdbe.org/6cmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cmj RCSB], [http://www.ebi.ac.uk/pdbsum/6cmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cmj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/KKCC2_HUMAN KKCC2_HUMAN]] Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching.<ref>PMID:11395482</ref> <ref>PMID:12935886</ref> <ref>PMID:9662074</ref> <ref>PMID:21957496</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood-brain barrier. When dosed orally in rodents, compound 4t limited ghrelin-induced food intake. | ||
| - | + | An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model.,Price DJ, Drewry DH, Schaller LT, Thompson BD, Reid PR, Maloney PR, Liang X, Banker P, Buckholz RG, Selley PK, McDonald OB, Smith JL, Shearer TW, Cox RF, Williams SP, Reid RA, Tacconi S, Faggioni F, Piubelli C, Sartori I, Tessari M, Wang TY Bioorg Med Chem Lett. 2018 Apr 5. pii: S0960-894X(18)30223-3. doi:, 10.1016/j.bmcl.2018.03.034. PMID:29653895<ref>PMID:29653895</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Reid, R | + | <div class="pdbe-citations 6cmj" style="background-color:#fffaf0;"></div> |
| - | [[Category: Williams, S | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Calcium/calmodulin-dependent protein kinase]] | ||
| + | [[Category: Human]] | ||
| + | [[Category: Drewry, D H]] | ||
| + | [[Category: Price, D J]] | ||
| + | [[Category: Reid, R A]] | ||
| + | [[Category: Williams, S P]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
Current revision
Human CAMKK2 with GSK650393
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