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2vr4

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[[Image:2vr4.png|left|200px]]
 
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{{STRUCTURE_2vr4| PDB=2vr4 | SCENE= }}
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==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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<StructureSection load='2vr4' size='340' side='right'caption='[[2vr4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<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>
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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]] 1.8&#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=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>
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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=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>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q8AAK6_BACTN Q8AAK6_BACTN]
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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/vr/2vr4_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=2vr4 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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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.
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===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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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>
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{{ABSTRACT_PUBMED_18408714}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2vr4" style="background-color:#fffaf0;"></div>
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[[2vr4]] is a 2 chain structure of [[Mannosidase]] with sequence from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VR4 OCA].
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==See Also==
==See Also==
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*[[Mannosidase|Mannosidase]]
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*[[Mannosidase 3D structures|Mannosidase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018408714</ref><references group="xtra"/>
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__TOC__
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[[Category: Bacteroides thetaiotaomicron]]
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</StructureSection>
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[[Category: Beta-mannosidase]]
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[[Category: Bacteroides thetaiotaomicron VPI-5482]]
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[[Category: Bleriot, Y.]]
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[[Category: Large Structures]]
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[[Category: Davies, G J.]]
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[[Category: Bleriot Y]]
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[[Category: Dumon, C.]]
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[[Category: Davies GJ]]
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[[Category: Gilbert, H J.]]
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[[Category: Dumon C]]
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[[Category: Gratien, J.]]
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[[Category: Gilbert HJ]]
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[[Category: Heck, M P.]]
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[[Category: Gratien J]]
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[[Category: Moreland, C.]]
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[[Category: Heck MP]]
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[[Category: Offen, W A.]]
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[[Category: Moreland C]]
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[[Category: Smith, N L.]]
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[[Category: Offen WA]]
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[[Category: Stick, R V.]]
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[[Category: Smith NL]]
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[[Category: Tailford, L E.]]
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[[Category: Stick RV]]
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[[Category: Vasella, A.]]
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[[Category: Tailford LE]]
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[[Category: Glycoside hydrolase]]
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[[Category: Vasella A]]
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[[Category: Hydrolase]]
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[[Category: Linear free energy relationship]]
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[[Category: Mannosidase]]
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[[Category: Transition state mimic]]
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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

PDB ID 2vr4

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