7uz2
From Proteopedia
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<table><tr><td colspan='2'>[[7uz2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus Saccharolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UZ2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uz2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus Saccharolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UZ2 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]] 1.83Å</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]] 1.83Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OML:( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OML:(1~{R},2~{S},3~{R},4~{R})-5-fluoranyl-6-(hydroxymethyl)cyclohex-5-ene-1,2,3,4-tetrol'>OML</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=7uz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uz2 OCA], [https://pdbe.org/7uz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uz2 RCSB], [https://www.ebi.ac.uk/pdbsum/7uz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uz2 ProSAT]</span></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=7uz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uz2 OCA], [https://pdbe.org/7uz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uz2 RCSB], [https://www.ebi.ac.uk/pdbsum/7uz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uz2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/BGAL_SACS2 BGAL_SACS2] |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Suitably configured allyl ethers of unsaturated cyclitols act as substrates of beta-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of beta-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus beta-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis. | Suitably configured allyl ethers of unsaturated cyclitols act as substrates of beta-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of beta-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus beta-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis. | ||
| - | Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors.,Danby PM, Jeong A, Sim L, Sweeney RP, Wardman JF, Karimi R, Geissner A, Worrall LJ, Reid JP, Strynadka NCJ, Withers | + | Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors.,Danby PM, Jeong A, Sim L, Sweeney RP, Wardman JF, Karimi R, Geissner A, Worrall LJ, Reid JP, Strynadka NCJ, Withers SG Angew Chem Int Ed Engl. 2023 May 15;62(21):e202301258. doi: , 10.1002/anie.202301258. Epub 2023 Apr 14. PMID:36940280<ref>PMID:36940280</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Structure of beta-glycosidase from Sulfolobus solfataricus in complex with C5a-fluoro-valienide.
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