2vmf: Difference between revisions

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-[[Image:2vmf.png|left|200px]]
-{{STRUCTURE_2vmf|  PDB=2vmf  |  SCENE=  }}
+==Structural and biochemical evidence for a boat-like transition state in beta-mannosidases==
+<StructureSection load='2vmf' size='340' side='right'caption='[[2vmf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2vmf]] 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=2VMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VMF 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]] 2.1&#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=MVL:(5R,6R,7S,8R)-5-(HYDROXYMETHYL)-5,6,7,8-TETRAHYDROIMIDAZO[1,2-A]PYRIDINE-6,7,8-TRIOL'>MVL</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=2vmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vmf OCA], [https://pdbe.org/2vmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vmf RCSB], [https://www.ebi.ac.uk/pdbsum/2vmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vmf 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/vm/2vmf_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=2vmf 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===
+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>
-{{ABSTRACT_PUBMED_18408714}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2vmf" style="background-color:#fffaf0;"></div>
-[[2vmf]] is a 2 chain structure 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=2VMF OCA].
 ==See Also==
-*[[Mannosidase|Mannosidase]]
+*[[Mannosidase 3D structures|Mannosidase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:018408714</ref><references group="xtra"/>
+__TOC__
-[[Category: Bacteroides thetaiotaomicron]]
+</StructureSection>
-[[Category: Beta-mannosidase]]
+[[Category: Bacteroides thetaiotaomicron VPI-5482]]
-[[Category: Bleriot, Y.]]
+[[Category: Large Structures]]
-[[Category: Davies, G J.]]
+[[Category: Bleriot Y]]
-[[Category: Dumon, C.]]
+[[Category: Davies GJ]]
-[[Category: Gilbert, H J.]]
+[[Category: Dumon C]]
-[[Category: Gratien, J.]]
+[[Category: Gilbert HJ]]
-[[Category: Heck, M P.]]
+[[Category: Gratien J]]
-[[Category: Moreland, C.]]
+[[Category: Heck MP]]
-[[Category: Offen, W A.]]
+[[Category: Moreland C]]
-[[Category: Smith, N L.]]
+[[Category: Offen WA]]
-[[Category: Stick, R V.]]
+[[Category: Smith NL]]
-[[Category: Tailford, L E.]]
+[[Category: Stick RV]]
-[[Category: Vasella, A.]]
+[[Category: Tailford LE]]
-[[Category: Glycoside hydrolase]]
+[[Category: Vasella A]]
-[[Category: Hydrolase]]
-[[Category: Linear free energy relationship]]
-[[Category: Mannosidase]]
-[[Category: Transition state mimic]]