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[[Image:2vqu.jpg|left|200px]]
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{{STRUCTURE_2vqu|  PDB=2vqu  |  SCENE=  }}
'''STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES'''


==Structural and biochemical evidence for a boat-like transition state in beta-mannosidases==
<StructureSection load='2vqu' size='340' side='right'caption='[[2vqu]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vqu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VQU 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]] 1.9&#8491;</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=NOY:(2R,3S,4R,5R)-5-(HYDROXYMETHYL)PIPERIDINE-2,3,4-TRIOL'>NOY</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=2vqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vqu OCA], [https://pdbe.org/2vqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vqu RCSB], [https://www.ebi.ac.uk/pdbsum/2vqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vqu 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/vq/2vqu_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=2vqu 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.


==Overview==
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>
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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2VQU is a [[Single protein]] structure of 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=2VQU OCA].
</div>
<div class="pdbe-citations 2vqu" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/18408714 18408714]
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacteroides thetaiotaomicron]]
[[Category: Bacteroides thetaiotaomicron]]
[[Category: Beta-mannosidase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Bleriot Y]]
[[Category: Bleriot, Y.]]
[[Category: Davies GJ]]
[[Category: Davies, G J.]]
[[Category: Dumon C]]
[[Category: Dumon, C.]]
[[Category: Gilbert HJ]]
[[Category: Gilbert, H J.]]
[[Category: Gratien J]]
[[Category: Gratien, J.]]
[[Category: Heck MP]]
[[Category: Heck, M P.]]
[[Category: Moreland C]]
[[Category: Moreland, C.]]
[[Category: Offen WA]]
[[Category: Offen, W A.]]
[[Category: Smith NL]]
[[Category: Smith, N L.]]
[[Category: Stick RV]]
[[Category: Stick, R V.]]
[[Category: Tailford LE]]
[[Category: Tailford, L E.]]
[[Category: Vasella A]]
[[Category: Vasella, A.]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase]]
[[Category: Linear free energy relationship]]
[[Category: Mannosidase]]
[[Category: Transition state mimic]]
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Retrieved from "https://proteopedia.org/2vqu"