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| | <StructureSection load='1w3k' size='340' side='right'caption='[[1w3k]], [[Resolution|resolution]] 1.20Å' scene=''> | | <StructureSection load='1w3k' size='340' side='right'caption='[[1w3k]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w3k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_700163 Atcc 700163]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W3K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w3k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Salipaludibacillus_agaradhaerens Salipaludibacillus agaradhaerens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W3K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W3K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OXZ:TETRAHYDROOXAZINE'>OXZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a3h|1a3h]], [[1h11|1h11]], [[1h2j|1h2j]], [[1h5v|1h5v]], [[1hf6|1hf6]], [[1ocq|1ocq]], [[1w3l|1w3l]], [[2a3h|2a3h]], [[3a3h|3a3h]], [[5a3h|5a3h]], [[6a3h|6a3h]], [[7a3h|7a3h]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OXZ:TETRAHYDROOXAZINE'>OXZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cellulase Cellulase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.4 3.2.1.4] </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=1w3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w3k OCA], [https://pdbe.org/1w3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w3k RCSB], [https://www.ebi.ac.uk/pdbsum/1w3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w3k 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=1w3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w3k OCA], [https://pdbe.org/1w3k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w3k RCSB], [https://www.ebi.ac.uk/pdbsum/1w3k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w3k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GUN5_SALAG GUN5_SALAG] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 700163]] | |
| - | [[Category: Cellulase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Davies, G J]] | + | [[Category: Salipaludibacillus agaradhaerens]] |
| - | [[Category: Gloster, T M]] | + | [[Category: Davies GJ]] |
| - | [[Category: Macdonald, J M]] | + | [[Category: Gloster TM]] |
| - | [[Category: Stick, R V]] | + | [[Category: Macdonald JM]] |
| - | [[Category: Tarling, C A]] | + | [[Category: Stick RV]] |
| - | [[Category: Withers, S W]] | + | [[Category: Tarling CA]] |
| - | [[Category: Cellulose degradation]] | + | [[Category: Withers SW]] |
| - | [[Category: Endoglucanase]]
| + | |
| - | [[Category: Family 5]]
| + | |
| - | [[Category: Glycoside hydrolase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Tetrahydrooxazine]]
| + | |
| Structural highlights
Function
GUN5_SALAG
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
The understanding of transition state mimicry in glycoside hydrolysis is increasingly important both in the quest for novel specific therapeutic agents and for the deduction of enzyme function and mechanism. To aid comprehension, inhibitors can be characterized through kinetic, thermodynamic, and structural dissection to build an "inhibition profile." Here we dissect the binding of a tetrahydrooxazine inhibitor and its derivatives, which display Ki values around 500 nm. X-ray structures with both a beta-glucosidase, at 2 A resolution, and an endoglucanase at atomic (approximately 1 A) resolution reveal similar interactions between the tetrahydrooxazine inhibitor and both enzymes. Kinetic analyses reveal the pH dependence of kcat/Km and 1/Ki with both enzyme systems, and isothermal titration calorimetry unveils the enthalpic and entropic contributions to beta-glucosidase inhibition. The pH dependence of enzyme activity mirrored that of 1/Ki in both enzymes, unlike the cases of isofagomine and 1-deoxynojirimycin that have been characterized previously. Calorimetric dissection reveals a large favorable enthalpy that is partially offset by an unfavorable entropy upon binding. In terms of the similar profile for the pH dependence of 1/Ki and the pH dependence of kcat/Km, the significant enthalpy of binding when compared with other glycosidase inhibitors, and the tight binding at the optimal pH of the enzymes tested, tetrahydrooxazine and its derivatives are a significantly better class of glycosidase inhibitor than previously assumed.
Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases.,Gloster TM, Macdonald JM, Tarling CA, Stick RV, Withers SG, Davies GJ J Biol Chem. 2004 Nov 19;279(47):49236-42. Epub 2004 Sep 8. PMID:15356002[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gloster TM, Macdonald JM, Tarling CA, Stick RV, Withers SG, Davies GJ. Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases. J Biol Chem. 2004 Nov 19;279(47):49236-42. Epub 2004 Sep 8. PMID:15356002 doi:10.1074/jbc.M407195200
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