2vot

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(New page: 200px {{Structure |PDB= 2vot |SIZE=350|CAPTION= <scene name='initialview01'>2vot</scene>, resolution 1.95&Aring; |SITE= <scene name='pdbsite=AC1:Binding+Site+For+...)
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[[Image:2vot.jpg|left|200px]]
 
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{{Structure
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==Structural and biochemical evidence for a boat-like transition state in beta-mannosidases==
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|PDB= 2vot |SIZE=350|CAPTION= <scene name='initialview01'>2vot</scene>, resolution 1.95&Aring;
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<StructureSection load='2vot' size='340' side='right'caption='[[2vot]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Binding+Site+For+Residue+Nhv+A+1865'>AC1</scene>, <scene name='pdbsite=AC2:Binding+Site+For+Residue+Edo+A+1866'>AC2</scene>, <scene name='pdbsite=AC3:Binding+Site+For+Residue+Edo+A+1867'>AC3</scene>, <scene name='pdbsite=AC4:Binding+Site+For+Residue+Edo+A+1868'>AC4</scene>, <scene name='pdbsite=AC5:Binding+Site+For+Residue+Edo+A+1869'>AC5</scene>, <scene name='pdbsite=AC6:Binding+Site+For+Residue+Edo+A+1870'>AC6</scene>, <scene name='pdbsite=AC7:Binding+Site+For+Residue+Edo+A+1871'>AC7</scene>, <scene name='pdbsite=AC8:Binding+Site+For+Residue+Edo+A+1872'>AC8</scene>, <scene name='pdbsite=AC9:Binding+Site+For+Residue+Edo+A+1873'>AC9</scene>, <scene name='pdbsite=BC1:Binding+Site+For+Residue+Edo+A+1874'>BC1</scene>, <scene name='pdbsite=BC2:Binding+Site+For+Residue+Edo+A+1875'>BC2</scene>, <scene name='pdbsite=BC3:Binding+Site+For+Residue+Edo+A+1876'>BC3</scene>, <scene name='pdbsite=BC4:Binding+Site+For+Residue+Edo+A+1877'>BC4</scene>, <scene name='pdbsite=BC5:Binding+Site+For+Residue+Edo+A+1878'>BC5</scene>, <scene name='pdbsite=BC6:Binding+Site+For+Residue+Edo+A+1879'>BC6</scene>, <scene name='pdbsite=BC7:Binding+Site+For+Residue+Edo+A+1880'>BC7</scene>, <scene name='pdbsite=BC8:Binding+Site+For+Residue+Edo+A+1881'>BC8</scene>, <scene name='pdbsite=BC9:Binding+Site+For+Residue+Edo+A+1882'>BC9</scene>, <scene name='pdbsite=CC1:Binding+Site+For+Residue+Edo+A+1883'>CC1</scene>, <scene name='pdbsite=CC2:Binding+Site+For+Residue+Edo+A+1884'>CC2</scene>, <scene name='pdbsite=CC3:Binding+Site+For+Residue+Edo+A+1885'>CC3</scene>, <scene name='pdbsite=CC4:Binding+Site+For+Residue+Br+A+1888'>CC4</scene>, <scene name='pdbsite=CC5:Binding+Site+For+Residue+Br+A+1889'>CC5</scene>, <scene name='pdbsite=CC6:Binding+Site+For+Residue+Nhv+B+1868'>CC6</scene>, <scene name='pdbsite=CC7:Binding+Site+For+Residue+Edo+B+1869'>CC7</scene>, <scene name='pdbsite=CC8:Binding+Site+For+Residue+Edo+B+1870'>CC8</scene>, <scene name='pdbsite=CC9:Binding+Site+For+Residue+Edo+B+1871'>CC9</scene>, <scene name='pdbsite=DC1:Binding+Site+For+Residue+Edo+B+1872'>DC1</scene>, <scene name='pdbsite=DC2:Binding+Site+For+Residue+Edo+B+1873'>DC2</scene>, <scene name='pdbsite=DC3:Binding+Site+For+Residue+Edo+B+1874'>DC3</scene>, <scene name='pdbsite=DC4:Binding+Site+For+Residue+Edo+B+1875'>DC4</scene>, <scene name='pdbsite=DC5:Binding+Site+For+Residue+Edo+B+1876'>DC5</scene>, <scene name='pdbsite=DC6:Binding+Site+For+Residue+Edo+B+1877'>DC6</scene>, <scene name='pdbsite=DC7:Binding+Site+For+Residue+Edo+B+1878'>DC7</scene>, <scene name='pdbsite=DC8:Binding+Site+For+Residue+Edo+B+1879'>DC8</scene>, <scene name='pdbsite=DC9:Binding+Site+For+Residue+Edo+B+1880'>DC9</scene>, <scene name='pdbsite=EC1:Binding+Site+For+Residue+Edo+B+1881'>EC1</scene>, <scene name='pdbsite=EC2:Binding+Site+For+Residue+Edo+B+1882'>EC2</scene>, <scene name='pdbsite=EC3:Binding+Site+For+Residue+Edo+B+1883'>EC3</scene>, <scene name='pdbsite=EC4:Binding+Site+For+Residue+Edo+B+1884'>EC4</scene>, <scene name='pdbsite=EC5:Binding+Site+For+Residue+Edo+B+1885'>EC5</scene>, <scene name='pdbsite=EC6:Binding+Site+For+Residue+Edo+B+1886'>EC6</scene>, <scene name='pdbsite=EC7:Binding+Site+For+Residue+Edo+B+1887'>EC7</scene>, <scene name='pdbsite=EC8:Binding+Site+For+Residue+Edo+B+1888'>EC8</scene>, <scene name='pdbsite=EC9:Binding+Site+For+Residue+Edo+B+1889'>EC9</scene>, <scene name='pdbsite=FC1:Binding+Site+For+Residue+Br+B+1890'>FC1</scene>, <scene name='pdbsite=FC2:Binding+Site+For+Residue+Br+B+1891'>FC2</scene>, <scene name='pdbsite=FC3:Binding+Site+For+Residue+Cl+B+1894'>FC3</scene>, <scene name='pdbsite=FC4:Binding+Site+For+Residue+Edo+B+1895'>FC4</scene>, <scene name='pdbsite=FC5:Binding+Site+For+Residue+Cl+B+1896'>FC5</scene>, <scene name='pdbsite=FC6:Binding+Site+For+Residue+Edo+A+1890'>FC6</scene>, <scene name='pdbsite=FC7:Binding+Site+For+Residue+Edo+B+1897'>FC7</scene>, <scene name='pdbsite=FC8:Binding+Site+For+Residue+Edo+B+1898'>FC8</scene>, <scene name='pdbsite=FC9:Binding+Site+For+Residue+Cl+B+1899'>FC9</scene>, <scene name='pdbsite=GC1:Binding+Site+For+Residue+Edo+A+1891'>GC1</scene>, <scene name='pdbsite=GC2:Binding+Site+For+Residue+Edo+A+1892'>GC2</scene>, <scene name='pdbsite=GC3:Binding+Site+For+Residue+Edo+B+1900'>GC3</scene>, <scene name='pdbsite=GC4:Binding+Site+For+Residue+Edo+B+1901'>GC4</scene>, <scene name='pdbsite=GC5:Binding+Site+For+Residue+Edo+A+1893'>GC5</scene>, <scene name='pdbsite=GC6:Binding+Site+For+Residue+Edo+B+1902'>GC6</scene> and <scene name='pdbsite=GC7:Binding+Site+For+Residue+Edo+A+1894'>GC7</scene>
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== Structural highlights ==
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|LIGAND= <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=NHV:(5R,6R,7S,8R)-6,7,8-TRIHYDROXY-5-(HYDROXYMETHYL)-2-[(PHENYLAMINO)METHYL]-5,6,7,8-TETRAHYDRO-1H-IMIDAZO[1,2-A]PYRIDIN-4-IUM'>NHV</scene>
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<table><tr><td colspan='2'>[[2vot]] 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=2VOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VOT FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-mannosidase Beta-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.25 3.2.1.25] </span>
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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]] 1.95&#8491;</td></tr>
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|GENE=
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<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=NHV:(5R,6R,7S,8R)-6,7,8-TRIHYDROXY-5-(HYDROXYMETHYL)-2-[(PHENYLAMINO)METHYL]-5,6,7,8-TETRAHYDRO-1H-IMIDAZO[1,2-A]PYRIDIN-4-IUM'>NHV</scene></td></tr>
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam02837 Glyco_hydro_2_N], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG3250 LacZ], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam02836 Glyco_hydro_2_C]</span>
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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=2vot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vot OCA], [https://pdbe.org/2vot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vot RCSB], [https://www.ebi.ac.uk/pdbsum/2vot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vot ProSAT]</span></td></tr>
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|RELATEDENTRY=[[2vqt|2VQT]], [[2vl4|2VL4]], [[2vqu|2VQU]], [[2vo5|2VO5]], [[2je8|2JE8]], [[2vjx|2VJX]], [[2vmf|2VMF]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vot OCA], [http://www.ebi.ac.uk/pdbsum/2vot PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vot RCSB]</span>
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== Function ==
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}}
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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/vo/2vot_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=2vot 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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'''STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES'''
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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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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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<div class="pdbe-citations 2vot" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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2VOT 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=2VOT OCA].
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*[[Mannosidase 3D structures|Mannosidase 3D structures]]
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[[Category: Bacteroides thetaiotaomicron]]
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== References ==
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[[Category: Beta-mannosidase]]
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<references/>
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[[Category: Single protein]]
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__TOC__
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[[Category: Bleriot, Y.]]
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</StructureSection>
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[[Category: Davies, G J.]]
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[[Category: Bacteroides thetaiotaomicron VPI-5482]]
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[[Category: Dumon, C.]]
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[[Category: Large Structures]]
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[[Category: Gilbert, H J.]]
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[[Category: Bleriot Y]]
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[[Category: Gratien, J.]]
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[[Category: Davies GJ]]
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[[Category: Heck, M P.]]
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[[Category: Dumon C]]
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[[Category: Moreland, C.]]
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[[Category: Gilbert HJ]]
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[[Category: Offen, W A.]]
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[[Category: Gratien J]]
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[[Category: Smith, N.]]
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[[Category: Heck M-P]]
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[[Category: Stick, R V.]]
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[[Category: Moreland C]]
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[[Category: Tailford, L N.]]
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[[Category: Offen WA]]
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[[Category: Vasella, A.]]
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[[Category: Smith N]]
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[[Category: glycoside hydrolase]]
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[[Category: Stick RV]]
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[[Category: hydrolase]]
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[[Category: Tailford LN]]
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[[Category: linear free energy relationship]]
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[[Category: Vasella A]]
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[[Category: mannosidase]]
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[[Category: transition state mimic]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:58:41 2008''
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Current revision

Structural and biochemical evidence for a boat-like transition state in beta-mannosidases

PDB ID 2vot

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