2vo5: Difference between revisions
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<StructureSection load='2vo5' size='340' side='right'caption='[[2vo5]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='2vo5' size='340' side='right'caption='[[2vo5]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vo5]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2vo5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bactn Bactn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VO5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VBZ:(1R,4R,5R,7R,8R)-2-BENZYL-5-HYDROXYMETHYL-2-AZA-BICYCLO[2.2.2]OCTANE-4,7,8-TRIOL'>VBZ</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=VBZ:(1R,4R,5R,7R,8R)-2-BENZYL-5-HYDROXYMETHYL-2-AZA-BICYCLO[2.2.2]OCTANE-4,7,8-TRIOL'>VBZ</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vqt|2vqt]], [[2vot|2vot]], [[2vl4|2vl4]], [[2vqu|2vqu]], [[2je8|2je8]], [[2vjx|2vjx]], [[2vmf|2vmf]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2vqt|2vqt]], [[2vot|2vot]], [[2vl4|2vl4]], [[2vqu|2vqu]], [[2je8|2je8]], [[2vjx|2vjx]], [[2vmf|2vmf]]</div></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-mannosidase Beta-mannosidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.25 3.2.1.25] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vo5 OCA], [https://pdbe.org/2vo5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vo5 RCSB], [https://www.ebi.ac.uk/pdbsum/2vo5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vo5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
Revision as of 14:41, 30 March 2022
Structural and biochemical evidence for a boat-like transition state in beta-mannosidasesStructural and biochemical evidence for a boat-like transition state in beta-mannosidases
Structural highlights
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 PubMedEnzyme inhibition through mimicry of the transition state is a major area for the design of new therapeutic agents. Emerging evidence suggests that many retaining glycosidases that are active on alpha- or beta-mannosides harness unusual B2,5 (boat) transition states. Here we present the analysis of 25 putative beta-mannosidase inhibitors, whose Ki values range from nanomolar to millimolar, on the Bacteroides thetaiotaomicron beta-mannosidase BtMan2A. B2,5 or closely related conformations were observed for all tightly binding compounds. Subsequent linear free energy relationships that correlate log Ki with log Km/kcat for a series of active center variants highlight aryl-substituted mannoimidazoles as powerful transition state mimics in which the binding energy of the aryl group enhances both binding and the degree of transition state mimicry. Support for a B2,5 transition state during enzymatic beta-mannosidase hydrolysis should also facilitate the design and exploitation of transition state mimics for the inhibition of retaining alpha-mannosidases--an area that is emerging for anticancer therapeutics. Structural and biochemical evidence for a boat-like transition state in beta-mannosidases.,Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Bleriot Y, Vasella A, Gilbert HJ, Davies GJ Nat Chem Biol. 2008 May;4(5):306-12. PMID:18408714[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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