2vl4: Difference between revisions
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==Structural and biochemical evidence for a boat-like transition state in beta-mannosidases== | |||
<StructureSection load='2vl4' size='340' side='right' caption='[[2vl4]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2vl4' size='340' side='right' caption='[[2vl4]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vqt|2vqt]], [[2vot|2vot]], [[2vqu|2vqu]], [[2vo5|2vo5]], [[2je8|2je8]], [[2vjx|2vjx]], [[2vmf|2vmf]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vqt|2vqt]], [[2vot|2vot]], [[2vqu|2vqu]], [[2vo5|2vo5]], [[2je8|2je8]], [[2vjx|2vjx]], [[2vmf|2vmf]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vl4 OCA], [http://pdbe.org/2vl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vl4 RCSB], [http://www.ebi.ac.uk/pdbsum/2vl4 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vl4 OCA], [http://pdbe.org/2vl4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vl4 RCSB], [http://www.ebi.ac.uk/pdbsum/2vl4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vl4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vl/2vl4_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vl/2vl4_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 00:08, 20 September 2018
Structural and biochemical evidence for a boat-like transition state in beta-mannosidasesStructural and biochemical evidence for a boat-like transition state in beta-mannosidases
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEnzyme 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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