The role of streptavidin and its variants in catalysis by biotinylated secondary amines
View/ Open
Impact
Scholar |
Other documents of the author: Nödling, Alexander; Santi, Nicolò; Castillo, Raquel; Lipka-Lloyd, Magdalena; Jin, Yi; Morrill, Louis; Świderek, Katarzyna; Moliner, Vicent; Luk, Louis Yu Pan
Metadata
Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7013
comunitat-uji-handle3:10234/8638
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
The role of streptavidin and its variants in catalysis by biotinylated secondary aminesAuthor (s)
Date
2021-11-15Publisher
Royal Society of ChemistryISSN
1477-0520Bibliographic 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.Type
info:eu-repo/semantics/articleVersion
info:eu-repo/semantics/publishedVersionSubject
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 ... [+]
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. [-]
Is part of
Organic & Biomolecular Chemistry. Issue 47 (December 2021)Funder Name
Ministerio de Ciencia, Innovación y Universidades | Cardiff School of Chemistry | Generalitat Valenciana | Universitat Jaume I | Leverhulme Trust | Royal Society | UK’s Wellcome Trust
Project code
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
Project title or grant
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
Rights
This journal is © The Royal Society of Chemistry 2021
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
This item appears in the folowing collection(s)
- QFA_Articles [819]