Communication

The Molecular Mechanism of Enzymatic Glycosyl Transfer with Retention of Configuration: Evidence for a Short-Lived Oxocarbenium-Like Species^†

Albert Ardèvol

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)

Search for more papers by this author

Prof. Carme Rovira,

Corresponding Author

Prof. Carme Rovira

[email protected]

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)

Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08020 Barcelona (Spain)

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)Search for more papers by this author

Albert Ardèvol,

Albert Ardèvol

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)

Search for more papers by this author

Prof. Carme Rovira,

Corresponding Author

Prof. Carme Rovira

[email protected]

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)

Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08020 Barcelona (Spain)

Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)Search for more papers by this author

First published: 26 September 2011

https://doi.org/10.1002/anie.201104623

Citations: 92

^†

We thank Prof. A. Planas, Prof. B. G. Davis, and Dr. S. S. Lee for enlightening discussions on the mechanisms of GTs. This work was funded by the MICINN (FIS2008-03845) and GENCAT (2009SGR-1309). A.A. thanks MEC for a FPU studentship. We acknowledge the computer support, technical expertise, and assistance provided by the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS).

Share a link

Email
Wechat
Bluesky

Graphical Abstract

A quantum leap: By means of quantum mechanics/molecular mechanics metadynamics simulations, a front-face S_Ni-type reaction for glycosyl transfer with retention of the anomeric configuration is shown to be feasible. A short-lived oxocarbenium-like species (see picture; O red, P gold, N blue, C black) is identified and provides the complete itinerary of this long sought after molecular mechanism.

Supporting Information

References

1D. J. Vocadlo, G. J. Davies, Curr. Opin. Chem. Biol. 2008, 12, 539–555.
10.1016/j.cbpa.2008.05.010
CAS PubMed Web of Science® Google Scholar
2L. L. Lairson, B. Henrissat, G. J. Davies, S. G. Withers, Annu. Rev. Biochem. 2008, 77, 521–555.
10.1146/annurev.biochem.76.061005.092322
CAS PubMed Web of Science® Google Scholar
3L. N. Gastinel, C. Bignon, A. K. Misra, O. Hindsgaul, J. H. Shaper, D. H. Joziasse, EMBO J. 2001, 20, 638–649.
10.1093/emboj/20.4.638
CAS PubMed Web of Science® Google Scholar
4A. Monegal, A. Planas, J. Am. Chem. Soc. 2006, 128, 16030–16031.
10.1021/ja0659931
CAS PubMed Web of Science® Google Scholar
5N. Soya, Y. Fang, M. M. Palcic, J. S. Klassen, Glycobiology 2011, 21, 547–552.
10.1093/glycob/cwq190
CAS PubMed Web of Science® Google Scholar
6I. Andre, I. Tvaroska, J. P. Carver, Carbohydr. Res. 2003, 338, 865–877.
10.1016/S0008-6215(03)00050-8
CAS PubMed Web of Science® Google Scholar
7M. L. Sinnott, Chem. Rev. 1990, 90, 1171–1202.
10.1021/cr00105a006
CAS Web of Science® Google Scholar
8K. Persson, H. D. Ly, M. Dieckelmann, W. W. Wakarchuk, S. G. Withers, N. C. Strynadka, Nat. Struct. Biol. 2001, 8, 166–175.
10.1038/84168
CAS PubMed Web of Science® Google Scholar
9M. L. Sinnott, W. P. Jencks, J. Am. Chem. Soc. 1980, 102, 2026–2032.
10.1021/ja00526a043
CAS Web of Science® Google Scholar
10
10aI. Tvaroška, Carbohydr. Res. 2004, 339, 1007–1014;
10.1016/j.carres.2003.11.014
CAS PubMed Web of Science® Google Scholar
10bI. Tvaroska in Molecular modeling of retaining glycosyltransferases, Vol. 930 (Eds.: ), American Chemical Society, Washington, 2006, pp. 285–301.
Web of Science® Google Scholar
11C. Goedl and B. Nidetzky, ChemBioChem 2009, 10, 2333–2337.
10.1002/cbic.200900429
CAS PubMed Web of Science® Google Scholar
12J. C. Errey, S. S. Lee, R. P. Gibson, C. Martinez Fleites, C. S. Barry, P. M. Jung, A. C. O’Sullivan, B. G. Davis, G. J. Davies, Angew. Chem. 2010, 122, 1256–1259;
10.1002/ange.200905096
Google Scholar
Angew. Chem. Int. Ed. 2010, 49, 1234–1237.
10.1002/anie.200905096
CAS PubMed Web of Science® Google Scholar
13S. S. Lee, S. Y. Hong, J. C. Errey, A. Izumi, G. J. Davies, B. G. Davis, Nat. Chem. Biol. 2011, DOI: .
Google Scholar
14A. Warshel, M. Levitt, J. Mol. Biol. 1976, 103, 227–249.
10.1016/0022-2836(76)90311-9
CAS PubMed Web of Science® Google Scholar
15A. Laio, M. Parrinello, Proc. Natl. Acad. Sci. USA 2002, 99, 12562–12566.
10.1073/pnas.202427399
CAS PubMed Web of Science® Google Scholar
16
16aM. Boero, T. Ikeda, E. Ito, K. Terakura, J. Am. Chem. Soc. 2006, 128, 16798–16807;
10.1021/ja064117k
CAS PubMed Web of Science® Google Scholar
16bV. Leone, F. Marinelli, P. Carloni, M. Parrinello, Curr. Opin. Struct. Biol. 2010, 20, 148–154.
10.1016/j.sbi.2010.01.011
CAS PubMed Web of Science® Google Scholar
17
17aL. Petersen, A. Ardevol, C. Rovira, P. J. Reilly, J. Phys. Chem. B 2009, 113, 7331–7339;
10.1021/jp811470d
CAS PubMed Web of Science® Google Scholar
17bL. Petersen, A. Ardevol, C. Rovira, P. J. Reilly, J. Am. Chem. Soc. 2010, 132, 8291–8300;
10.1021/ja909249u
CAS PubMed Web of Science® Google Scholar
17cI. J. Barker, L. Petersen, P. J. Reilly, J. Phys. Chem. B 2010, 114, 15389–15393.
10.1021/jp107886e
CAS PubMed Web of Science® Google Scholar
18W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graph. 1996, 14, 33–38.
10.1016/0263-7855(96)00018-5
CAS PubMed Web of Science® Google Scholar
19H. S. Seo, Y. J. Koo, J. Y. Lim, J. T. Song, C. H. Kim, J. K. Kim, J. S. Lee, Y. D. Choi, Appl. Environ. Microbiol. 2000, 66, 2484–2490.
10.1128/AEM.66.6.2484-2490.2000
CAS PubMed Web of Science® Google Scholar
20K. Fukui, Acc. Chem. Res. 1981, 14, 363–368.
10.1021/ar00072a001
CAS Web of Science® Google Scholar
21A. Laio, J. VandeVondele, U. Rothlisberger, J. Chem. Phys. 2002, 116, 6941–6947.
10.1063/1.1462041
CAS Web of Science® Google Scholar
22R. Car, M. Parrinello, Phys. Rev. Lett. 1985, 55, 2471–2474.
10.1103/PhysRevLett.55.2471
CAS PubMed Web of Science® Google Scholar
23Y. K. Zhang, T. S. Lee, W. T. Yang, J. Chem. Phys. 1999, 110, 46–54.
10.1063/1.478083
CAS PubMed Web of Science® Google Scholar
24J. P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 1996, 77, 3865–3868.
10.1103/PhysRevLett.77.3865
CAS PubMed Web of Science® Google Scholar
25X. Biarnes, J. Nieto, A. Planas, C. Rovira, J. Biol. Chem. 2006, 281, 1432–1441.
10.1074/jbc.M507643200
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume50, Issue46

November 11, 2011

Pages 10897-10901

The Molecular Mechanism of Enzymatic Glycosyl Transfer with Retention of Configuration: Evidence for a Short-Lived Oxocarbenium-Like Species^†

Graphical Abstract

Supporting Information

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

The Molecular Mechanism of Enzymatic Glycosyl Transfer with Retention of Configuration: Evidence for a Short-Lived Oxocarbenium-Like Species†

Graphical Abstract

Supporting Information

References

Citing Literature

References

Related

Information

The Molecular Mechanism of Enzymatic Glycosyl Transfer with Retention of Configuration: Evidence for a Short-Lived Oxocarbenium-Like Species^†