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==Structure of an E333Q variant of the GH99 endo-alpha-mannanase from Bacteroides xylanisolvens in complex with alpha-1,3-mannobiose and alpha-1,2-mannobiose== | ==Structure of an E333Q variant of the GH99 endo-alpha-mannanase from Bacteroides xylanisolvens in complex with alpha-1,3-mannobiose and alpha-1,2-mannobiose== | ||
<StructureSection load='6fwq' size='340' side='right'caption='[[6fwq]]' scene=''> | <StructureSection load='6fwq' size='340' side='right'caption='[[6fwq]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FWQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6FWQ FirstGlance]. <br> | <table><tr><td colspan='2'>[[6fwq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacteroides_sp._xb1a Bacteroides sp. xb1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FWQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6FWQ FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6fwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwq OCA], [http://pdbe.org/6fwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fwq RCSB], [http://www.ebi.ac.uk/pdbsum/6fwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwq ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fwg|6fwg]], [[6fwi|6fwi]], [[6fwj|6fwj]], [[6fwl|6fwl]], [[6fwm|6fwm]], [[6fwo|6fwo]], [[6fwp|6fwp]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BXY_34140 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=657309 Bacteroides sp. XB1A])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6fwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwq OCA], [http://pdbe.org/6fwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fwq RCSB], [http://www.ebi.ac.uk/pdbsum/6fwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwq ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Retaining glycoside hydrolases cleave their substrates through stereochemical retention at the anomeric position. Typically, this involves two-step mechanisms using either an enzymatic nucleophile via a covalent glycosyl enzyme intermediate or neighboring-group participation by a substrate-borne 2-acetamido neighboring group via an oxazoline intermediate; no enzymatic mechanism with participation of the sugar 2-hydroxyl has been reported. Here, we detail structural, computational, and kinetic evidence for neighboring-group participation by a mannose 2-hydroxyl in glycoside hydrolase family 99 endo-alpha-1,2-mannanases. We present a series of crystallographic snapshots of key species along the reaction coordinate: a Michaelis complex with a tetrasaccharide substrate; complexes with intermediate mimics, a sugar-shaped cyclitol beta-1,2-aziridine and beta-1,2-epoxide; and a product complex. The 1,2-epoxide intermediate mimic displayed hydrolytic and transfer reactivity analogous to that expected for the 1,2-anhydro sugar intermediate supporting its catalytic equivalence. Quantum mechanics/molecular mechanics modeling of the reaction coordinate predicted a reaction pathway through a 1,2-anhydro sugar via a transition state in an unusual flattened, envelope (E 3) conformation. Kinetic isotope effects (k cat/K M) for anomeric-(2)H and anomeric-(13)C support an oxocarbenium ion-like transition state, and that for C2-(18)O (1.052 +/- 0.006) directly implicates nucleophilic participation by the C2-hydroxyl. Collectively, these data substantiate this unprecedented and long-imagined enzymatic mechanism. | |||
An Epoxide Intermediate in Glycosidase Catalysis.,Sobala LF, Speciale G, Zhu S, Raich L, Sannikova N, Thompson AJ, Hakki Z, Lu D, Shamsi Kazem Abadi S, Lewis AR, Rojas-Cervellera V, Bernardo-Seisdedos G, Zhang Y, Millet O, Jimenez-Barbero J, Bennet AJ, Sollogoub M, Rovira C, Davies GJ, Williams SJ ACS Cent Sci. 2020 May 27;6(5):760-770. doi: 10.1021/acscentsci.0c00111. Epub, 2020 Apr 16. PMID:32490192<ref>PMID:32490192</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6fwq" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacteroides sp. xb1a]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bennet A]] | [[Category: Bennet, A]] | ||
[[Category: Bernardo-Seisdedos G]] | [[Category: Bernardo-Seisdedos, G]] | ||
[[Category: Davies | [[Category: Davies, G J]] | ||
[[Category: Fernandes | [[Category: Fernandes, P Z]] | ||
[[Category: Hakki Z]] | [[Category: Hakki, Z]] | ||
[[Category: Jimenez-Barbero J]] | [[Category: Jimenez-Barbero, J]] | ||
[[Category: Lu D]] | [[Category: Lu, D]] | ||
[[Category: Millet O]] | [[Category: Millet, O]] | ||
[[Category: Raich L]] | [[Category: Raich, L]] | ||
[[Category: Rojas-Cervellera V]] | [[Category: Rojas-Cervellera, V]] | ||
[[Category: Rovira C]] | [[Category: Rovira, C]] | ||
[[Category: Sobala | [[Category: Sobala, L F]] | ||
[[Category: Sollogoub M]] | [[Category: Sollogoub, M]] | ||
[[Category: Speciale G]] | [[Category: Speciale, G]] | ||
[[Category: Thompson | [[Category: Thompson, A J]] | ||
[[Category: Williams | [[Category: Williams, S J]] | ||
[[Category: Zhu S]] | [[Category: Zhu, S]] | ||
[[Category: Hydrolase]] | |||