Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/229762
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Self-Immolation of a Bacterial Dehydratase Enzyme by its Epoxide Product |
Autor: | Lence, Emilio; Maneiro, María; Sanz‐Gaitero, Marta; van Raaij, Mark J. CSIC ORCID ; Thompson, Paul; Hawkins, Alastair R.; González‐Bello, Concepción | Palabras clave: | Enzymatic mechanisms Epoxide proforms Lysine-covalent modification Reaction intermediates Structural enzymology |
Fecha de publicación: | 26-jun-2020 | Editor: | John Wiley & Sons | Citación: | Chemistry - A European Journal 26(36): 8035-8044 (2020) | Resumen: | Disabling the bacterial capacity to cause infection is an innovative approach that has attracted significant attention to fight against superbugs. A relevant target for anti‐virulence drug discovery is the type I dehydroquinase (DHQ1) enzyme. It was shown that the 2‐hydroxyethylammonium derivative 3 has in vitro activity since it causes the covalent modification of the catalytic lysine residue of DHQ1. As this compound does not bear reactive electrophilic centers, how the chemical modification occurs is intriguing. We report here an integrated approach, which involves biochemical studies, X‐ray crystallography and computational studies on the reaction path using combined quantum mechanics/molecular mechanics Umbrella Sampling Molecular Dynamics, that evidences that DHQ1 catalyzes its self‐immolation by transforming the unreactive 2‐hydroxyethylammonium group in 3 into an epoxide that triggers the lysine covalent modification. This finding might open opportunities for the design of lysine‐targeted irreversible inhibitors bearing a 2‐hydroxyethylammonium moiety as an epoxide proform, which to our knowledge has not been reported previously. | Versión del editor: | http://dx.doi.org/10.1002/chem.202000759 | URI: | http://hdl.handle.net/10261/229762 | DOI: | 10.1002/chem.202000759 | ISSN: | 0947-6539 | E-ISSN: | 1521-3765 |
Aparece en las colecciones: | (CNB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
2
checked on 07-may-2024
WEB OF SCIENCETM
Citations
2
checked on 29-feb-2024
Page view(s)
78
checked on 15-may-2024
Download(s)
12
checked on 15-may-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.