5ox4: Difference between revisions
New page: '''Unreleased structure''' The entry 5ox4 is ON HOLD until Paper Publication Authors: Kyriakis, E., Stravodimos, G.A., Kantsadi, A.L., Chatzileontiadou, D.S.M., Leonidas, D.D. Descript... |
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==Glycogen Phosphorylase in complex with CK900== | |||
<StructureSection load='5ox4' size='340' side='right'caption='[[5ox4]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ox4]] 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=5OX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OX4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B1W:(2~{S},3~{R},4~{R},5~{S},6~{R})-2-[5-(4-aminophenyl)-4~{H}-1,2,4-triazol-3-yl]-6-(hydroxymethyl)oxane-3,4,5-triol'>B1W</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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=5ox4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ox4 OCA], [https://pdbe.org/5ox4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ox4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ox4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ox4 ProSAT]</span></td></tr> | |||
</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 == | |||
Human liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism, is a valid pharmaceutical target for the development of new anti-hyperglycaemic agents for type 2 diabetes. Inhibitor discovery studies have focused on the active site and in particular on glucopyranose based compounds with a beta-1 substituent long enough to exploit interactions with a cavity adjacent to the active site, termed the beta-pocket. Recently, C-beta-d-glucopyranosyl imidazoles and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of hlGP. Here we probe the beta-pocket by studying the inhibitory effect of six different groups at the para position of 3-(beta-d-glucopyranosyl phenyl)-5-phenyl-, 1, 2, 4-triazoles in hlGP by kinetics and X-ray crystallography. The most bioactive compound was the one with an amine substituent to show a Ki value of 0.43muM. Structural studies have revealed the physicochemical diversity of the beta-pocket providing information for future rational inhibitor design studies. | |||
Probing the beta-pocket of the active site of human liver glycogen phosphorylase with 3-(C-beta-d-glucopyranosyl)-5-(4-substituted-phenyl)-1, 2, 4-triazole inhibitors.,Kyriakis E, Solovou TGA, Kun S, Czifrak K, Szocs B, Juhasz L, Bokor E, Stravodimos GA, Kantsadi AL, Chatzileontiadou DSM, Skamnaki VT, Somsak L, Leonidas DD Bioorg Chem. 2018 Feb 12;77:485-493. doi: 10.1016/j.bioorg.2018.02.008. PMID:29454281<ref>PMID:29454281</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ox4" style="background-color:#fffaf0;"></div> | ||
[[Category: Kantsadi | |||
[[Category: | ==See Also== | ||
[[Category: Leonidas | *[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]] | ||
[[Category: Stravodimos | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Chatzileontiadou DSM]] | |||
[[Category: Kantsadi AL]] | |||
[[Category: Kyriakis E]] | |||
[[Category: Leonidas DD]] | |||
[[Category: Stravodimos GA]] | |||
Latest revision as of 04:27, 28 December 2023
Glycogen Phosphorylase in complex with CK900Glycogen Phosphorylase in complex with CK900
Structural highlights
FunctionPYGM_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. Publication Abstract from PubMedHuman liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism, is a valid pharmaceutical target for the development of new anti-hyperglycaemic agents for type 2 diabetes. Inhibitor discovery studies have focused on the active site and in particular on glucopyranose based compounds with a beta-1 substituent long enough to exploit interactions with a cavity adjacent to the active site, termed the beta-pocket. Recently, C-beta-d-glucopyranosyl imidazoles and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of hlGP. Here we probe the beta-pocket by studying the inhibitory effect of six different groups at the para position of 3-(beta-d-glucopyranosyl phenyl)-5-phenyl-, 1, 2, 4-triazoles in hlGP by kinetics and X-ray crystallography. The most bioactive compound was the one with an amine substituent to show a Ki value of 0.43muM. Structural studies have revealed the physicochemical diversity of the beta-pocket providing information for future rational inhibitor design studies. Probing the beta-pocket of the active site of human liver glycogen phosphorylase with 3-(C-beta-d-glucopyranosyl)-5-(4-substituted-phenyl)-1, 2, 4-triazole inhibitors.,Kyriakis E, Solovou TGA, Kun S, Czifrak K, Szocs B, Juhasz L, Bokor E, Stravodimos GA, Kantsadi AL, Chatzileontiadou DSM, Skamnaki VT, Somsak L, Leonidas DD Bioorg Chem. 2018 Feb 12;77:485-493. doi: 10.1016/j.bioorg.2018.02.008. PMID:29454281[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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