2vr4
From Proteopedia
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| - | [[Image:2vr4.png|left|200px]] | ||
| - | + | ==Transition-state mimicry in mannoside hydrolysis: characterisation of twenty six inhibitors and insight into binding from linear free energy relationships and 3-D structure== | |
| + | <StructureSection load='2vr4' size='340' side='right'caption='[[2vr4]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2vr4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VR4 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=17B:(2Z,3R,4S,5R,6R)-2-[(4-AMINOBUTYL)IMINO]-6-(HYDROXYMETHYL)PIPERIDINE-3,4,5-TRIOL'>17B</scene>, <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></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=2vr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vr4 OCA], [https://pdbe.org/2vr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vr4 RCSB], [https://www.ebi.ac.uk/pdbsum/2vr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vr4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q8AAK6_BACTN Q8AAK6_BACTN] | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/2vr4_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=2vr4 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Enzyme 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<ref>PMID:18408714</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2vr4" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Mannosidase|Mannosidase]] | + | *[[Mannosidase 3D structures|Mannosidase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: Bacteroides thetaiotaomicron]] | + | </StructureSection> |
| - | [[Category: | + | [[Category: Bacteroides thetaiotaomicron VPI-5482]] |
| - | [[Category: Bleriot | + | [[Category: Large Structures]] |
| - | [[Category: Davies | + | [[Category: Bleriot Y]] |
| - | [[Category: Dumon | + | [[Category: Davies GJ]] |
| - | [[Category: Gilbert | + | [[Category: Dumon C]] |
| - | [[Category: Gratien | + | [[Category: Gilbert HJ]] |
| - | [[Category: Heck | + | [[Category: Gratien J]] |
| - | [[Category: Moreland | + | [[Category: Heck MP]] |
| - | [[Category: Offen | + | [[Category: Moreland C]] |
| - | [[Category: Smith | + | [[Category: Offen WA]] |
| - | [[Category: Stick | + | [[Category: Smith NL]] |
| - | [[Category: Tailford | + | [[Category: Stick RV]] |
| - | [[Category: Vasella | + | [[Category: Tailford LE]] |
| - | + | [[Category: Vasella A]] | |
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Current revision
Transition-state mimicry in mannoside hydrolysis: characterisation of twenty six inhibitors and insight into binding from linear free energy relationships and 3-D structure
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