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| | <StructureSection load='3np7' size='340' side='right'caption='[[3np7]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='3np7' size='340' side='right'caption='[[3np7]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3np7]] 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=3NP7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NP7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3np7]] 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=3NP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NP7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z15:(1S)-1,5-ANHYDRO-1-(4-CHLORO-2,5-DIHYDROXYPHENYL)-D-GLUCITOL'>Z15</scene>, <scene name='pdbligand=Z16:(1S)-1,5-ANHYDRO-1-(3-CHLORO-2,5-DIHYDROXYPHENYL)-D-GLUCITOL'>Z16</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]] 2.05Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=Z15:(1S)-1,5-ANHYDRO-1-(4-CHLORO-2,5-DIHYDROXYPHENYL)-D-GLUCITOL'>Z15</scene>, <scene name='pdbligand=Z16:(1S)-1,5-ANHYDRO-1-(3-CHLORO-2,5-DIHYDROXYPHENYL)-D-GLUCITOL'>Z16</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3np9|3np9]], [[3npa|3npa]]</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=3np7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3np7 OCA], [https://pdbe.org/3np7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3np7 RCSB], [https://www.ebi.ac.uk/pdbsum/3np7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3np7 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3np7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3np7 OCA], [http://pdbe.org/3np7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3np7 RCSB], [http://www.ebi.ac.uk/pdbsum/3np7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3np7 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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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Phosphorylase]]
| + | [[Category: Alexacou K-M]] |
| - | [[Category: Alexacou, K M]] | + | |
| - | [[Category: Glycogenolysis]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| - | [[Category: Type 2 diabetes]]
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| 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
Electrophilic halogenation of C-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl) 1,4-dimethoxybenzene (1) afforded regioselectively products halogenated at the para position to the d-glucosyl moiety (8, 9) that were deacetylated to 3 (chloride) and 16 (bromide). For preparing meta regioisomers, 1 was efficiently oxidized with CAN to afford C-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl) 1,4-benzoquinone 2 which, in either MeOH or H(2)O-THF containing few equivalents of AcCl, added hydrochloric acid to produce predominantly meta (with respect to the sugar moiety) chlorinated hydroquinone derivatives 5 and 18, this latter being deacetylated to 4. The deacetylated meta (4, 5) or para (3, 16) halohydroquinones were evaluated as inhibitors of glycogen phosphorylase (GP, a molecular target for inhibition of hepatic glycogenolysis under high glucose concentrations) by kinetics and X-ray crystallography. These compounds are competitive inhibitors of GPb with respect to alpha-d-glucose-1-phosphate. The measured IC(50) values (muM) [169.9+/-10.0 (3), 95 (4), 39.8+/-0.3 (5) 136.4+/-4.9 (16)] showed that the meta halogenated inhibitors (4, 5) are more potent than their para analogs (3, 16). The crystal structures of GPb in complex with these compounds at high resolution (1.97-2.05A) revealed that the inhibitors are accommodated at the catalytic site and stabilize the T conformation of the enzyme. The differences in their inhibitory potency can be interpreted in terms of variations in the interactions with protein residues of the different substituents on the aromatic part of the inhibitors.
Halogen-substituted (C-beta-d-glucopyranosyl)-hydroquinone regioisomers: Synthesis, enzymatic evaluation and their binding to glycogen phosphorylase.,Alexacou KM, Zhang YZ, Praly JP, Zographos SE, Chrysina ED, Oikonomakos NG, Leonidas DD Bioorg Med Chem. 2011 Sep 1;19(17):5125-36. Epub 2011 Jul 26. PMID:21821421[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Alexacou KM, Zhang YZ, Praly JP, Zographos SE, Chrysina ED, Oikonomakos NG, Leonidas DD. Halogen-substituted (C-beta-d-glucopyranosyl)-hydroquinone regioisomers: Synthesis, enzymatic evaluation and their binding to glycogen phosphorylase. Bioorg Med Chem. 2011 Sep 1;19(17):5125-36. Epub 2011 Jul 26. PMID:21821421 doi:10.1016/j.bmc.2011.07.024
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