7q5i
From Proteopedia
(Difference between revisions)
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==A glucose-based molecular rotor probes the catalytic site of glycogen phosphorylase.== | ==A glucose-based molecular rotor probes the catalytic site of glycogen phosphorylase.== | ||
- | <StructureSection load='7q5i' size='340' side='right'caption='[[7q5i]]' scene=''> | + | <StructureSection load='7q5i' size='340' side='right'caption='[[7q5i]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q5I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7q5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q5I FirstGlance]. <br> |
- | </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=7q5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q5i OCA], [https://pdbe.org/7q5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q5i RCSB], [https://www.ebi.ac.uk/pdbsum/7q5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q5i ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=I0F:2-cyano-3-[4-(dimethylamino)phenyl]-~{N}-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]propanamide'>I0F</scene></td></tr> |
+ | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | ||
+ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </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=7q5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q5i OCA], [https://pdbe.org/7q5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q5i RCSB], [https://www.ebi.ac.uk/pdbsum/7q5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q5i ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | == Function == | ||
+ | [[https://www.uniprot.org/uniprot/PYGM_RABIT PYGM_RABIT]] Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Molecular rotors belong to a family of fluorescent compounds characterized as molecular switches, where a fluorescence on/off signal signifies a change in the molecule's microenvironment. Herein, the successful synthesis and detailed study of (E)-2-cyano-3-(p-(dimethylamino)phenyl)-N-(beta-D-glucopyranosyl)acrylamide (RotA), is reported. RotA was found to be a strong inhibitor of rabbit muscle glycogen phosphorylase (RMGPb), that binds at the catalytic site of the enzyme. RotA's interactions with the residues lining the catalytic site of RMGPb were determined by X-ray crystallography. Spectroscopic studies coupled with theoretical calculations proved that RotA is a molecular rotor. When bound in the catalytic channel of RMGPb, it behaved as a light switch, generating a strong fluorescence signal, allowing utilization of RotA as a probe that locates glycogen phosphorylase (GP). RotA, mono-, di- and per-acetylated derivatives, as well as nanoparticles with RotA encapsulated in polyethylene glycol-poly-L-histidine, were used in live cell fluorescence microscopy imaging to test the delivery of RotA through the plasma membrane of HepG2 and A431 cells, with the nanoparticles providing the best results. Once in the intracellular milieu, RotA exhibits remarkable colocalization with GP and significant biological effects, both in cell growth and inhibition of GP. | ||
+ | |||
+ | A glucose-based molecular rotor inhibitor of glycogen phosphorylase as a probe of cellular enzymatic function.,Minadakis MP, Mavreas KF, Neofytos DD, Paschou M, Kogkaki A, Athanasiou V, Mamais M, Veclani D, Iatrou H, Venturini A, Chrysina ED, Papazafiri P, Gimisis T Org Biomol Chem. 2022 Feb 4. doi: 10.1039/d1ob02211c. PMID:35119451<ref>PMID:35119451</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 7q5i" style="background-color:#fffaf0;"></div> | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: Chrysina | + | [[Category: Oryctolagus cuniculus]] |
- | [[Category: Neofytos | + | [[Category: Phosphorylase]] |
+ | [[Category: Chrysina, E D]] | ||
+ | [[Category: Neofytos, D D]] | ||
+ | [[Category: Glycogen phosphorylase]] | ||
+ | [[Category: Inhibitor]] | ||
+ | [[Category: Molecular rotor]] | ||
+ | [[Category: Sugar binding protein]] | ||
+ | [[Category: Type 2 diabetes]] |
Revision as of 07:24, 9 March 2022
A glucose-based molecular rotor probes the catalytic site of glycogen phosphorylase.
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