1hlf

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[[Image:1hlf.gif|left|200px]]
 
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==BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD==
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The line below this paragraph, containing "STRUCTURE_1hlf", creates the "Structure Box" on the page.
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<StructureSection load='1hlf' size='340' side='right'caption='[[1hlf]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1hlf]] 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=1HLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HLF FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GL4:8,9,10-TRIHYDROXY-7-HYDROXYMETHYL-2-THIOXO-6-OXA-1,3-DIAZA-SPIRO[4.5]DECAN-4-ONE'>GL4</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
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{{STRUCTURE_1hlf| PDB=1hlf | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hlf OCA], [https://pdbe.org/1hlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hlf RCSB], [https://www.ebi.ac.uk/pdbsum/1hlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hlf ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hl/1hlf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1hlf ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Glucopyranosylidene spirothiohydantoin (TH) has been identified as a potential inhibitor of both muscle and liver glycogen phosphorylase b (GPb) and a (GPa) and shown to diminish liver GPa activity in vitro. Kinetic experiments reported here show that TH inhibits muscle GPb competitively with respect to both substrates phosphate (K(i)=2.3 microM) and glycogen (K(i)=2.8 microM). The structure of the GPb-TH complex has been determined at a resolution of 2.26 A and refined to a crystallographic R value of 0.193 (R(free)=0.211). The structure of GPb-TH complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change of the tertiary structure, and provides a basis of understanding potency and specificity of the inhibitor. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the glucose complex, while the rigid thiohydantoin group is in a favourable electrostatic environment and makes additional polar contacts to the protein.
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'''BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD'''
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Kinetic and crystallographic studies of glucopyranosylidene spirothiohydantoin binding to glycogen phosphorylase B.,Oikonomakos NG, Skamnaki VT, Osz E, Szilagyi L, Somsak L, Docsa T, Toth B, Gergely P Bioorg Med Chem. 2002 Feb;10(2):261-8. PMID:11741774<ref>PMID:11741774</ref>
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==Overview==
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Glucopyranosylidene spirothiohydantoin (TH) has been identified as a potential inhibitor of both muscle and liver glycogen phosphorylase b (GPb) and a (GPa) and shown to diminish liver GPa activity in vitro. Kinetic experiments reported here show that TH inhibits muscle GPb competitively with respect to both substrates phosphate (K(i)=2.3 microM) and glycogen (K(i)=2.8 microM). The structure of the GPb-TH complex has been determined at a resolution of 2.26 A and refined to a crystallographic R value of 0.193 (R(free)=0.211). The structure of GPb-TH complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change of the tertiary structure, and provides a basis of understanding potency and specificity of the inhibitor. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the glucose complex, while the rigid thiohydantoin group is in a favourable electrostatic environment and makes additional polar contacts to the protein.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1HLF is a [[Single protein]] structure of 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=1HLF OCA].
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</div>
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<div class="pdbe-citations 1hlf" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Kinetic and crystallographic studies of glucopyranosylidene spirothiohydantoin binding to glycogen phosphorylase B., Oikonomakos NG, Skamnaki VT, Osz E, Szilagyi L, Somsak L, Docsa T, Toth B, Gergely P, Bioorg Med Chem. 2002 Feb;10(2):261-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11741774 11741774]
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*[[Glycogen phosphorylase 3D structures|Glycogen phosphorylase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
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[[Category: Phosphorylase]]
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[[Category: Docsa T]]
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[[Category: Single protein]]
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[[Category: Gergely P]]
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[[Category: Docsa, T.]]
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[[Category: Oikonomakos NG]]
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[[Category: Gergely, P.]]
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[[Category: Osz E]]
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[[Category: Oikonomakos, N G.]]
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[[Category: Skamnaki VT]]
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[[Category: Osz, E.]]
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[[Category: Somsak L]]
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[[Category: Skamnaki, V T.]]
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[[Category: Szilagyi L]]
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[[Category: Somsak, L.]]
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[[Category: Toth B]]
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[[Category: Szilagyi, L.]]
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[[Category: Toth, B.]]
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[[Category: Catalytic site]]
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[[Category: Design]]
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[[Category: Glycogen phosphorylase]]
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[[Category: Inhibitor complex]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:58:53 2008''
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Current revision

BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD

PDB ID 1hlf

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