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The role of streptavidin and its variants in catalysis by biotinylated secondary amines
dc.contributor.author | Nödling, Alexander | |
dc.contributor.author | Santi, Nicolò | |
dc.contributor.author | Castillo, Raquel | |
dc.contributor.author | Lipka-Lloyd, Magdalena | |
dc.contributor.author | Jin, Yi | |
dc.contributor.author | Morrill, Louis | |
dc.contributor.author | Świderek, Katarzyna | |
dc.contributor.author | Moliner, Vicent | |
dc.contributor.author | Luk, Louis Yu Pan | |
dc.date.accessioned | 2022-02-02T18:15:30Z | |
dc.date.available | 2022-02-02T18:15:30Z | |
dc.date.issued | 2021-11-15 | |
dc.identifier.citation | Nödling, Alexander R., et al. "The role of streptavidin and its variants in catalysis by biotinylated secondary amines." Organic & biomolecular chemistry 19.47 (2021): 10424-10431. | ca_CA |
dc.identifier.issn | 1477-0520 | |
dc.identifier.uri | http://hdl.handle.net/10234/196617 | |
dc.description.abstract | Here, we combine the use of host screening, protein crystallography and QM/MM molecular dynamics simulations to investigate how the protein structure affects iminium catalysis by biotinylated secondary amines in a model 1,4 conjugate addition reaction. Monomeric streptavidin (M-Sav) lacks a quaternary structure and the solvent-exposed reaction site resulted in poor product conversion in the model reaction with low enantio- and regioselectivities. These parameters were much improved when the tetrameric host T-Sav was used; indeed, residues at the symmetrical subunit interface were proven to be critical for catalysis through a mutagenesis study. The use of QM/MM simulations and the asymmetric dimeric variant D-Sav revealed that both Lys121 residues which are located in the hosting and neighboring subunits play a critical role in controlling the stereoselectivity and reactivity. Lastly, the D-Sav template, though providing a lower conversion than that of the symmetric tetrameric counterpart, is likely a better starting point for future protein engineering because each surrounding residue within the asymmetric scaffold can be refined for secondary amine catalysis. | ca_CA |
dc.format.extent | 8 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | Royal Society of Chemistry | ca_CA |
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dc.relation | Unravelling the Reaction and Inhibition Mechanism of Proteasome 20S and Rhomboid Protease by QM/MM Theoretical Methods: Two Bio-Macromolecules Involved in Cancer Proliferation | |
dc.relation | Diseño de nuevas enzimas mediante el uso de métodos computacionales multiescala | |
dc.relation.isPartOf | Organic & Biomolecular Chemistry. Issue 47 (December 2021) | ca_CA |
dc.rights | This journal is © The Royal Society of Chemistry 2021 | ca_CA |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | ca_CA |
dc.subject | catalysis | ca_CA |
dc.subject | biotinylated secondary amines | ca_CA |
dc.title | The role of streptavidin and its variants in catalysis by biotinylated secondary amines | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.1039/D1OB01947C | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
project.funder.name | Ministerio de Ciencia, Innovación y Universidades | ca_CA |
project.funder.name | Cardiff School of Chemistry | ca_CA |
project.funder.name | Generalitat Valenciana | ca_CA |
project.funder.name | Universitat Jaume I | ca_CA |
project.funder.name | Leverhulme Trust | ca_CA |
project.funder.name | Royal Society | ca_CA |
project.funder.name | UK’s Wellcome Trust | ca_CA |
oaire.awardNumber | PGC2018-094852-B-C21 | ca_CA |
oaire.awardNumber | PID2019-107098RJ-I00 | ca_CA |
oaire.awardNumber | AICO/2019/ 195 | ca_CA |
oaire.awardNumber | SEJI/2020/007 | ca_CA |
oaire.awardNumber | UJI·B2017-31 | ca_CA |
oaire.awardNumber | UJI-A2019-04 | ca_CA |
oaire.awardNumber | RPG-2017-195 | ca_CA |
oaire.awardNumber | RG150466 | ca_CA |
oaire.awardNumber | 202056/Z/16/Z | ca_CA |
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