5owz: Difference between revisions

Latest revision as of 01:27, 28 December 2023

Glycogen Phosphorylase in complex with KS172

Structural highlights

5owz is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.85Å
Ligands:	B0Z, IMP, PLP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. 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. Bioorg Chem. 2018 Feb 12;77:485-493. doi: 10.1016/j.bioorg.2018.02.008. PMID:29454281 doi:https://dx.doi.org/10.1016/j.bioorg.2018.02.008

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OCA

[1] 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. 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. Bioorg Chem. 2018 Feb 12;77:485-493. doi: 10.1016/j.bioorg.2018.02.008. PMID:29454281 doi:https://dx.doi.org/10.1016/j.bioorg.2018.02.008

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5owz' size='340' side='right'caption='[[5owz]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5owz]] 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=5OWZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OWZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5owz]] 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=5OWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OWZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B0Z:(2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-[5-[4-(trifluoromethyl)phenyl]-4~{H}-1,2,4-triazol-3-yl]oxane-3,4,5-triol'>B0Z</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</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]] 1.85&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5owy|5owy]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B0Z:(2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-[5-[4-(trifluoromethyl)phenyl]-4~{H}-1,2,4-triazol-3-yl]oxane-3,4,5-triol'>B0Z</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5owz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5owz OCA], [https://pdbe.org/5owz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5owz RCSB], [https://www.ebi.ac.uk/pdbsum/5owz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5owz ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5owz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5owz OCA], [http://pdbe.org/5owz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5owz RCSB], [http://www.ebi.ac.uk/pdbsum/5owz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5owz ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 29: / Line 28: @@
 [[Category: Large Structures]]
 [[Category: Oryctolagus cuniculus]]
-[[Category: Phosphorylase]]
+[[Category: Chatzileontiadou DSM]]
-[[Category: Chatzileontiadou, D S.M]]
+[[Category: Kantsadi AL]]
-[[Category: Kantsadi, A L]]
+[[Category: Kyriakis E]]
-[[Category: Kyriakis, E]]
+[[Category: Leonidas DD]]
-[[Category: Leonidas, D D]]
+[[Category: Stravodimos GA]]
-[[Category: Stravodimos, G A]]
-[[Category: Transferase]]

5owz: Difference between revisions

Latest revision as of 01:27, 28 December 2023

Glycogen Phosphorylase in complex with KS172

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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