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5i3d
From Proteopedia
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<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=5i3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3d OCA], [http://pdbe.org/5i3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3d RCSB], [http://www.ebi.ac.uk/pdbsum/5i3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3d ProSAT]</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=5i3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3d OCA], [http://pdbe.org/5i3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3d RCSB], [http://www.ebi.ac.uk/pdbsum/5i3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3d ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SNi-like mechanisms, which involve front-face leaving group departure and nucleophile approach, have been observed experimentally and computationally in chemical and enzymatic substitution at alpha-glycosyl electrophiles. Since SNi-like, SN1 and SN2 substitution pathways can be energetically comparable, engineered switching could be feasible. Here, engineering of Sulfolobus solfataricus beta-glycosidase, which originally catalyzed double SN2 substitution, changed its mode to SNi-like. Destruction of the first SN2 nucleophile through E387Y mutation created a beta-stereoselective catalyst for glycoside synthesis from activated substrates, despite lacking a nucleophile. The pH profile, kinetic and mutational analyses, mechanism-based inactivators, X-ray structure and subsequent metadynamics simulations together suggest recruitment of substrates by pi-sugar interaction and reveal a quantum mechanics-molecular mechanics (QM/MM) free-energy landscape for the substitution reaction that is similar to those of natural, SNi-like glycosyltransferases. This observation of a front-face mechanism in a beta-glycosyltransfer enzyme highlights that SNi-like pathways may be engineered in catalysts with suitable environments and suggests that 'beta-SNi' mechanisms may be feasible for natural glycosyltransfer enzymes. | ||
| + | |||
| + | A front-face 'SNi synthase' engineered from a retaining 'double-SN2' hydrolase.,Iglesias-Fernandez J, Hancock SM, Lee SS, Khan M, Kirkpatrick J, Oldham NJ, McAuley K, Fordham-Skelton A, Rovira C, Davis BG Nat Chem Biol. 2017 Jun 12. doi: 10.1038/nchembio.2394. PMID:28604696<ref>PMID:28604696</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5i3d" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Galactosidase|Galactosidase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 11:00, 3 August 2017
Sulfolobus solfataricus beta-glycosidase - E387Y mutant
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