RT Journal Article
T1 Reaction mechanism of nucleoside 2′-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate
A1 Arco, Jon del
A1 Perona Requena, Almudena
A1 González, Leticia
A1 Fernández-Lucas, Jesús
A1 Gago, Federico
A1 Sánchez-Murcia, Pedro A.
AB Insight into the catalytic mechanism of Lactobacillus leichmannii nucleoside 2’-deoxyribosyltransferase (LlNDT) has been gained by calculating a quantum mechanics–molecular mechanics (QM/MM) freeenergy landscape of the reaction within the enzyme active site. Our results support an oxocarbenium species as the reaction intermediate and thus an SN1 reaction mechanism in this family of bacterial enzymes. Our mechanistic proposal is validated by comparing experimental kinetic data on the impact of the single amino acid replacements Tyr7, Glu98 and Met125 with Ala, Asp and Ala/norLeu, respectively, and accounts for the specificity shown by this enzyme on a non-natural substrate. This work broadens our understanding of enzymatic C–N bond cleavage and C–N bond formation.
PB Royal Society of Chemistry
SN 1477-0520
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/97640
UL https://hdl.handle.net/20.500.14352/97640
LA eng
NO Org. Biomol. Chem., 2019, 17, 7891–7899
NO Fondo Austriaco para la Ciencia(FWF)
NO Ministerio de Economía, Comercio y Empresa(España)
NO Fundación Banco Santander
DS Docta Complutense
RD 8 abr 2025