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3ebp

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Revision as of 10:21, 9 September 2020

Glycogen Phosphorylase b/flavopiridol complex

Structural highlights

3ebp 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.
Ligands:
NonStd Res:
Related:	1c8k, 1e1y, 3ebo
Activity:	Phosphorylase, with EC number 2.4.1.1
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.

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 PubMed

Flavonoids have been discovered as novel inhibitors of glycogen phosphorylase (GP), a target to control hyperglycemia in type 2 diabetes. To elucidate the mechanism of inhibition, we have determined the crystal structure of the GPb-chrysin complex at 1.9A resolution. Chrysin is accommodated at the inhibitor site intercalating between the aromatic side chains of Phe285 and Tyr613 through pi-stacking interactions. Chrysin binds to GPb approximately 15 times weaker (K(i)=19.01muM) than flavopiridol (K(i)=1.24muM), exclusively at the inhibitor site, and both inhibitors display similar behavior with respect to AMP. To identify the source of flavopiridols' stronger affinity, molecular docking with Glide and postdocking binding free energy calculations using QM/MM-PBSA have been performed and compared. Whereas docking failed to correctly rank inhibitor binding conformations, the QM/MM-PBSA method employing M06-2X/6-31+G(*) to model the pi-stacking interactions correctly reproduced the experimental results. Flavopiridols' greater binding affinity is sourced to favorable interactions of the cationic 4-hydroxypiperidin-1-yl substituent with GPb, with desolvation effects limited by the substituent conformation adopted in the crystallographic complex. Further successful predictions using QM/MM-PBSA for the flavonoid quercetagetin (which binds at the allosteric site) leads us to propose the methodology as a useful and inexpensive tool to predict flavonoid binding.

Sourcing the affinity of flavonoids for the glycogen phosphorylase inhibitor site via crystallography, kinetics and QM/MM-PBSA binding studies: Comparison of chrysin and flavopiridol.,Tsitsanou KE, Hayes JM, Keramioti M, Mamais M, Oikonomakos NG, Kato A, Leonidas DD, Zographos SE Food Chem Toxicol. 2012 Dec 29. pii: S0278-6915(12)00903-9. doi:, 10.1016/j.fct.2012.12.030. PMID:23279842^[1]

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

References

↑ Tsitsanou KE, Hayes JM, Keramioti M, Mamais M, Oikonomakos NG, Kato A, Leonidas DD, Zographos SE. Sourcing the affinity of flavonoids for the glycogen phosphorylase inhibitor site via crystallography, kinetics and QM/MM-PBSA binding studies: Comparison of chrysin and flavopiridol. Food Chem Toxicol. 2012 Dec 29. pii: S0278-6915(12)00903-9. doi:, 10.1016/j.fct.2012.12.030. PMID:23279842 doi:http://dx.doi.org/10.1016/j.fct.2012.12.030

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ebp"

@@ Line 1: / Line 1: @@
 ==Glycogen Phosphorylase b/flavopiridol complex==
-<StructureSection load='3ebp' size='340' side='right' caption='[[3ebp]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3ebp' size='340' side='right'caption='[[3ebp]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ebp]] 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=3EBP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3EBP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ebp]] 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=3EBP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3EBP FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPB:2-(2-CHLORO-PHENYL)-5,7-DIHYDROXY-8-(3-HYDROXY-1-METHYL-PIPERIDIN-4-YL)-4H-BENZOPYRAN-4-ONE'>CPB</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPB:2-(2-CHLORO-PHENYL)-5,7-DIHYDROXY-8-(3-HYDROXY-1-METHYL-PIPERIDIN-4-YL)-4H-BENZOPYRAN-4-ONE'>CPB</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c8k|1c8k]], [[1e1y|1e1y]], [[3ebo|3ebo]]</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=3ebp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ebp OCA], [http://pdbe.org/3ebp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ebp RCSB], [http://www.ebi.ac.uk/pdbsum/3ebp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ebp 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=3ebp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ebp OCA], [http://pdbe.org/3ebp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ebp RCSB], [http://www.ebi.ac.uk/pdbsum/3ebp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ebp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 33: / Line 33: @@
 ==See Also==
-*[[Glycogen Phosphorylase|Glycogen Phosphorylase]]
+*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Oryctolagus cuniculus]]
 [[Category: Phosphorylase]]

3ebp

From Proteopedia

Revision as of 10:21, 9 September 2020

Glycogen Phosphorylase b/flavopiridol complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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