2ffr: Difference between revisions
Jump to navigation
Jump to search
New page: left|200px<br /><applet load="2ffr" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ffr, resolution 2.03Å" /> '''Crystallographic stu... |
No edit summary |
||
| (18 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Crystallographic studies on N-azido-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamine== | ||
N-acetyl-beta-D-glucopyranosylamine (NAG) is a potent inhibitor (Ki=32 | <StructureSection load='2ffr' size='340' side='right'caption='[[2ffr]], [[Resolution|resolution]] 2.03Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ffr]] 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=2FFR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FFR 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]] 2.03Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DL6:2-AZIDO-N-((2R,3R,4S,5S,6R)-3,4,5-TRIHYDROXY-6-(HYDROXYMETHYL)-TETRAHYDRO-2H-PYRAN-2-YL)ACETAMIDE'>DL6</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=2ffr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ffr OCA], [https://pdbe.org/2ffr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ffr RCSB], [https://www.ebi.ac.uk/pdbsum/2ffr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ffr 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. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ff/2ffr_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ffr ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N-acetyl-beta-D-glucopyranosylamine (NAG) is a potent inhibitor (Ki=32 microM) of glycogen phosphorylase b (GPb), and has been employed as a lead compound for the structure-based design of new analogues, in an effort to utilize its potential as a hypoglycaemic agent. Replacement of the acetamido group by azidoacetamido group resulted in an inhibitor, N-azidoacetyl-beta-D-glucopyranosylamine (azido-NAG), with a Ki value of 48.7 microM, in the direction of glycogen synthesis. In order to elucidate the mechanism of inhibition, we determined the ligand structure in complex with GPb at 2.03 A resolution, and the structure of the fully acetylated derivative in the free form. The molecular packing of the latter is stabilized by a number of bifurcated hydrogen bonds of which the one involving a bifurcated C-H...N...H-C type hydrogen bonding is rather unique in organic azides. Azido-NAG can be accommodated in the catalytic site of T-state GPb at approximately the same position as that of NAG and stabilizes the T-state conformation of the 280 s loop by making several favourable contacts to residues of this loop. The difference observed in the Ki values of the two analogues can be interpreted in terms of desolvation effects, subtle structural changes of protein residues and changes in water structure. | |||
Crystallographic studies on N-azidoacetyl-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamine.,Petsalakis EI, Chrysina ED, Tiraidis C, Hadjiloi T, Leonidas DD, Oikonomakos NG, Aich U, Varghese B, Loganathan D Bioorg Med Chem. 2006 Aug 1;14(15):5316-24. Epub 2006 Apr 17. PMID:16616506<ref>PMID:16616506</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ffr" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Aich U]] | |||
[[Category: Chrysina ED]] | |||
[[Category: Aich | [[Category: Hadjiloi T]] | ||
[[Category: Chrysina | [[Category: Leonidas DD]] | ||
[[Category: Hadjiloi | [[Category: Loganathan D]] | ||
[[Category: Leonidas | [[Category: Oikonomakos NG]] | ||
[[Category: Loganathan | [[Category: Petsalakis EI]] | ||
[[Category: Oikonomakos | [[Category: Tiraidis C]] | ||
[[Category: Petsalakis | [[Category: Varghese B]] | ||
[[Category: Tiraidis | |||
[[Category: Varghese | |||
Latest revision as of 12:26, 30 August 2023
Crystallographic studies on N-azido-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamineCrystallographic studies on N-azido-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamine
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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedN-acetyl-beta-D-glucopyranosylamine (NAG) is a potent inhibitor (Ki=32 microM) of glycogen phosphorylase b (GPb), and has been employed as a lead compound for the structure-based design of new analogues, in an effort to utilize its potential as a hypoglycaemic agent. Replacement of the acetamido group by azidoacetamido group resulted in an inhibitor, N-azidoacetyl-beta-D-glucopyranosylamine (azido-NAG), with a Ki value of 48.7 microM, in the direction of glycogen synthesis. In order to elucidate the mechanism of inhibition, we determined the ligand structure in complex with GPb at 2.03 A resolution, and the structure of the fully acetylated derivative in the free form. The molecular packing of the latter is stabilized by a number of bifurcated hydrogen bonds of which the one involving a bifurcated C-H...N...H-C type hydrogen bonding is rather unique in organic azides. Azido-NAG can be accommodated in the catalytic site of T-state GPb at approximately the same position as that of NAG and stabilizes the T-state conformation of the 280 s loop by making several favourable contacts to residues of this loop. The difference observed in the Ki values of the two analogues can be interpreted in terms of desolvation effects, subtle structural changes of protein residues and changes in water structure. Crystallographic studies on N-azidoacetyl-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamine.,Petsalakis EI, Chrysina ED, Tiraidis C, Hadjiloi T, Leonidas DD, Oikonomakos NG, Aich U, Varghese B, Loganathan D Bioorg Med Chem. 2006 Aug 1;14(15):5316-24. Epub 2006 Apr 17. PMID:16616506[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||