The role of streptavidin and its variants in catalysis by biotinylated secondary amines
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Otros documentos de la autoría: Nödling, Alexander; Santi, Nicolò; Castillo, Raquel; Lipka-Lloyd, Magdalena; Jin, Yi; Morrill, Louis; Świderek, Katarzyna; Moliner, Vicent; Luk, Louis Yu Pan
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Título
The role of streptavidin and its variants in catalysis by biotinylated secondary aminesAutoría
Fecha de publicación
2021-11-15Editor
Royal Society of ChemistryISSN
1477-0520Cita bibliográfica
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.Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
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 ... [+]
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. [-]
Publicado en
Organic & Biomolecular Chemistry. Issue 47 (December 2021)Entidad financiadora
Ministerio de Ciencia, Innovación y Universidades | Cardiff School of Chemistry | Generalitat Valenciana | Universitat Jaume I | Leverhulme Trust | Royal Society | UK’s Wellcome Trust
Código del proyecto o subvención
PGC2018-094852-B-C21 | PID2019-107098RJ-I00 | AICO/2019/ 195 | SEJI/2020/007 | UJI·B2017-31 | UJI-A2019-04 | RPG-2017-195 | RG150466 | 202056/Z/16/Z
Título del proyecto o subvención
QMCUBE: Una plataforma universal para simulaciones multiescala en sistemas biológicos. Interpretando y prediciendo la actividad enzimática | Estudios computacionales del mecanismo y la inhibición de la proteólisis enzimática como enfoque complementario del mundo del descubrimiento moderno de fármacos | Diseño computacional de nuevos biocatalizadores | Unravelling the Reaction and Inhibition Mechanism of Proteasome 20S and Rhomboid Protease by QM/MM Theoretical Methods: Two Bio-Macromolecules Involved in Cancer Proliferation | Diseño de nuevas enzimas mediante el uso de métodos computacionales multiescala
Derechos de acceso
This journal is © The Royal Society of Chemistry 2021
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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