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| | <StructureSection load='4cto' size='340' side='right'caption='[[4cto]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='4cto' size='340' side='right'caption='[[4cto]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cto]] 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=4CTO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CTO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cto]] 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=4CTO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CTO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M7C:N-[(2Z,5R,7R,8S,9S,10R)-8,9,10-TRIHYDROXY-7-(HYDROXYMETHYL)-4-OXO-6-OXA-1-THIA-3-AZASPIRO[4.5]DEC-2-YLIDENE]BENZAMIDE'>M7C</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M7C:N-[(2Z,5R,7R,8S,9S,10R)-8,9,10-TRIHYDROXY-7-(HYDROXYMETHYL)-4-OXO-6-OXA-1-THIA-3-AZASPIRO[4.5]DEC-2-YLIDENE]BENZAMIDE'>M7C</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ctm|4ctm]], [[4ctn|4ctn]]</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=4cto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cto OCA], [https://pdbe.org/4cto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cto RCSB], [https://www.ebi.ac.uk/pdbsum/4cto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cto 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=4cto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cto OCA], [http://pdbe.org/4cto PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cto RCSB], [http://www.ebi.ac.uk/pdbsum/4cto PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cto 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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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Glycogen Phosphorylase|Glycogen Phosphorylase]] | + | *[[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: Alexacou KM]] |
| - | [[Category: Alexacou, K M]] | + | [[Category: Chrysina ED]] |
| - | [[Category: Chrysina, E D]] | + | [[Category: Leonidas DD]] |
| - | [[Category: Leonidas, D D]] | + | [[Category: Papakonstantinou M]] |
| - | [[Category: Papakonstantinou, M]] | + | [[Category: Zographos SE]] |
| - | [[Category: Zographos, S E]] | + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Structure-based drug design]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Type 2 diabetes]]
| + | |
| 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
The reaction of thiourea with O-perbenzoylated C-(1-bromo-1-deoxy-beta-d-glucopyranosyl)formamide gave the new anomeric spirocycle 1R-1,5-anhydro-d-glucitol-spiro-[1,5]-2-imino-1,3-thiazolidin-4-one. Acylation and sulfonylation with the corresponding acyl chlorides (RCOCl or RSO2Cl where R=tBu, Ph, 4-Me-C6H4, 1- and 2-naphthyl) produced the corresponding 2-acylimino- and 2-sulfonylimino-thiazolidinones, respectively. Alkylation by MeI, allyl-bromide and BnBr produced mixtures of the respective N-alkylimino- and N,N'-dialkyl-imino-thiazolidinones, while reactions with 1,2-dibromoethane and 1,3-dibromopropane furnished spirocyclic 5,6-dihydro-imidazo[2,1-b]thiazolidin-3-one and 6,7-dihydro-5H-thiazolidino[3,2-a]pyrimidin-3-one, respectively. Removal of the O-benzoyl protecting groups by the Zemplen protocol led to test compounds most of which proved micromolar inhibitors of rabbit muscle glycogen phosphorylase b (RMGPb). Best inhibitors were the 2-benzoylimino- (Ki=9muM) and the 2-naphthoylimino-thiazolidinones (Ki=10muM). Crystallographic studies of the unsubstituted spiro-thiazolidinone and the above most efficient inhibitors in complex with RMGPb confirmed the preference and inhibitory effect that aromatic (and especially 2-naphthyl) derivatives show for the catalytic site promoting the inactive conformation of the enzyme.
Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: Synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods.,Czifrak K, Pahi A, Deak S, Kiss-Szikszai A, Kover KE, Docsa T, Gergely P, Alexacou KM, Papakonstantinou M, Leonidas DD, Zographos SE, Chrysina ED, Somsak L Bioorg Med Chem. 2014 Aug 1;22(15):4028-41. doi: 10.1016/j.bmc.2014.05.076. Epub , 2014 Jun 16. PMID:25009003[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Czifrak K, Pahi A, Deak S, Kiss-Szikszai A, Kover KE, Docsa T, Gergely P, Alexacou KM, Papakonstantinou M, Leonidas DD, Zographos SE, Chrysina ED, Somsak L. Glucopyranosylidene-spiro-iminothiazolidinone, a new bicyclic ring system: Synthesis, derivatization, and evaluation for inhibition of glycogen phosphorylase by enzyme kinetic and crystallographic methods. Bioorg Med Chem. 2014 Aug 1;22(15):4028-41. doi: 10.1016/j.bmc.2014.05.076. Epub , 2014 Jun 16. PMID:25009003 doi:http://dx.doi.org/10.1016/j.bmc.2014.05.076
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