4mqu: Difference between revisions

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 ==Human GKRP complexed to AMG-3969 and S6P==
-<StructureSection load='4mqu' size='340' side='right' caption='[[4mqu]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
+<StructureSection load='4mqu' size='340' side='right'caption='[[4mqu]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4mqu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MQU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4mqu]] is a 2 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=4MQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MQU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG9:2-{4-[(2S)-4-[(6-AMINOPYRIDIN-3-YL)SULFONYL]-2-(PROP-1-YN-1-YL)PIPERAZIN-1-YL]PHENYL}-1,1,1,3,3,3-HEXAFLUOROPROPAN-2-OL'>MG9</scene>, <scene name='pdbligand=S6P:D-SORBITOL-6-PHOSPHATE'>S6P</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]] 2.22&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mro|4mro]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG9:2-{4-[(2S)-4-[(6-AMINOPYRIDIN-3-YL)SULFONYL]-2-(PROP-1-YN-1-YL)PIPERAZIN-1-YL]PHENYL}-1,1,1,3,3,3-HEXAFLUOROPROPAN-2-OL'>MG9</scene>, <scene name='pdbligand=S6P:D-SORBITOL-6-PHOSPHATE'>S6P</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mqu RCSB], [http://www.ebi.ac.uk/pdbsum/4mqu PDBsum]</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=4mqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqu OCA], [https://pdbe.org/4mqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mqu RCSB], [https://www.ebi.ac.uk/pdbsum/4mqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mqu ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GCKR_HUMAN GCKR_HUMAN]] Inhibits glucokinase by forming an inactive complex with this enzyme.
+[https://www.uniprot.org/uniprot/GCKR_HUMAN GCKR_HUMAN] Inhibits glucokinase by forming an inactive complex with this enzyme.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-In the previous report , we described the discovery and optimization of novel small molecule disruptors of the GK-GKRP interaction culminating in the identification of 1 (AMG-1694). Although this analogue possessed excellent in vitro potency and was a useful tool compound in initial proof-of-concept experiments, high metabolic turnover limited its advancement. Guided by a combination of metabolite identification and structure-based design, we have successfully discovered a potent and metabolically stable GK-GKRP disruptor (27, AMG-3969). When administered to db/db mice, this compound demonstrated a robust pharmacodynamic response (GK translocation) as well as statistically significant dose-dependent reductions in fed blood glucose levels.
-Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles.,St Jean DJ Jr, Ashton KS, Bartberger MD, Chen J, Chmait S, Cupples R, Galbreath E, Helmering J, Hong FT, Jordan SR, Liu L, Kunz RK, Michelsen K, Nishimura N, Pennington LD, Poon SF, Reid D, Sivits G, Stec MM, Tadesse S, Tamayo N, Van G, Yang KC, Zhang J, Norman MH, Fotsch C, Lloyd DJ, Hale C J Med Chem. 2014 Jan 23;57(2):325-38. doi: 10.1021/jm4016747. Epub 2014 Jan 9. PMID:24405213<ref>PMID:24405213</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+==See Also==
-</div>
+*[[Glucokinase Regulatory Protein|Glucokinase Regulatory Protein]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Ashton, K S]]
+[[Category: Homo sapiens]]
-[[Category: Bartberger, M D]]
+[[Category: Large Structures]]
-[[Category: Chen, J]]
+[[Category: Ashton KS]]
-[[Category: Chmait, S]]
+[[Category: Bartberger MD]]
-[[Category: Cupples, R]]
+[[Category: Chen J]]
-[[Category: Galbreath, E]]
+[[Category: Chmait S]]
-[[Category: Helmering, J]]
+[[Category: Cupples R]]
-[[Category: Jean, D J.St]]
+[[Category: Galbreath E]]
-[[Category: Jordan, S R]]
+[[Category: Helmering J]]
-[[Category: Liu, L]]
+[[Category: Jordan SR]]
-[[Category: Binds fructose phosphates and glucokinase]]
+[[Category: Liu L]]
-[[Category: Regulatory protein]]
+[[Category: St Jean DJ]]
-[[Category: Sis domain]]
-[[Category: Transferase inhibitor]]