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| | <StructureSection load='6s52' size='340' side='right'caption='[[6s52]], [[Resolution|resolution]] 2.37Å' scene=''> | | <StructureSection load='6s52' size='340' side='right'caption='[[6s52]], [[Resolution|resolution]] 2.37Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6s52]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S52 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S52 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6s52]] 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=6S52 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S52 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KVN:(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-(5-phenyl-1,2,3,4-tetrazol-2-yl)oxane-3,4,5-triol'>KVN</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2.37Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KVN:(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-(5-phenyl-1,2,3,4-tetrazol-2-yl)oxane-3,4,5-triol'>KVN</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6s52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s52 OCA], [http://pdbe.org/6s52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s52 RCSB], [http://www.ebi.ac.uk/pdbsum/6s52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s52 ProSAT]</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=6s52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s52 OCA], [https://pdbe.org/6s52 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s52 RCSB], [https://www.ebi.ac.uk/pdbsum/6s52 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s52 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6s52" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6s52" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Phosphorylase]]
| + | [[Category: Kyriakis E]] |
| - | [[Category: Kyriakis, E]] | + | [[Category: Leonidas DD]] |
| - | [[Category: Leonidas, D D]] | + | [[Category: Papaioannou OSE]] |
| - | [[Category: Papaioannou, O S.E]] | + | [[Category: Skamnaki VT]] |
| - | [[Category: Skamnaki, V T]] | + | [[Category: Solovou TGA]] |
| - | [[Category: Solovou, T G.A]] | + | |
| - | [[Category: C-beta-d-glucopyranosyl tetrazole]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
C-Glucopyranosyl imidazoles, thiazoles, and an N-glucopyranosyl tetrazole were assessed in vitro and ex vivo for their inhibitory efficiency against isoforms of glycogen phosphorylase (GP; a validated pharmacological target for the development of anti-hyperglycaemic agents). Imidazoles proved to be more potent inhibitors than the corresponding thiazoles or the tetrazole. The most potent derivative has a 2-naphthyl substituent, a Ki value of 3.2 microM for hepatic glycogen phosphorylase, displaying also 60% inhibition of GP activity in HepG2 cells, compared to control vehicle treated cells, at 100 muM. X-Ray crystallography studies of the protein - inhibitor complexes revealed the importance of the architecture of inhibitor associated hydrogen bonds or sulfur sigma-hole bond interactions to Asn284 OD1, offering new insights to structure-based design efforts. Moreover, while the 2-glucopyranosyl-tetrazole seems to bind differently from the corresponding 1,2,3-triazole compound, the two inhibitors are equipotent.
The architecture of hydrogen and sulfur sigma-hole interactions explain differences in the inhibitory potency of C-beta-d-glucopyranosyl thiazoles, imidazoles and an N-beta-d glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design.,Kyriakis E, Karra AG, Papaioannou O, Solovou T, Skamnaki VT, Liggri PGV, Zographos SE, Szennyes E, Bokor E, Kun S, Psarra AG, Somsak L, Leonidas DD Bioorg Med Chem. 2020 Jan 1;28(1):115196. doi: 10.1016/j.bmc.2019.115196. Epub, 2019 Nov 14. PMID:31767404[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kyriakis E, Karra AG, Papaioannou O, Solovou T, Skamnaki VT, Liggri PGV, Zographos SE, Szennyes E, Bokor E, Kun S, Psarra AG, Somsak L, Leonidas DD. The architecture of hydrogen and sulfur sigma-hole interactions explain differences in the inhibitory potency of C-beta-d-glucopyranosyl thiazoles, imidazoles and an N-beta-d glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design. Bioorg Med Chem. 2020 Jan 1;28(1):115196. doi: 10.1016/j.bmc.2019.115196. Epub, 2019 Nov 14. PMID:31767404 doi:http://dx.doi.org/10.1016/j.bmc.2019.115196
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