Miniatura

Fitxers

640941.pdf (1.36 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2014-01-20

Llicència de publicació

cc-by (c) Williams, Rohan J. et al., 2014
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/122754

Combined inhibitor free-energy landscape and structural analysis reports on the mannosidase conformational coordinate

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1002/anie.201308334

Resum

Mannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence‐based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X‐ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole‐type inhibitors are energetically poised to report faithfully on mannosidase transition‐state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including β‐mannanases from families GH26 and GH113. Isofagomine‐type inhibitors are poor mimics of transition‐state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar‐shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active‐site residues involved in substrate recognition.

Matèries

Enzims, Catàlisi, Anàlisi conformacional, Inhibidors enzimàtics

Matèries (anglès)

Enzymes, Catalysis, Conformational analysis, Enzyme inhibitors

Citació

Col·leccions

Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

WILLIAMS, Rohan j., IGLESIAS-FERNÁNDEZ, Javier, STEPPER, Judith, JACKSON, Adam, THOMPSON, Andrew j., LOWE, Elisabeth c., WHITE, Jonathan m., GILBERT, Harry j., ROVIRA I VIRGILI, Carme, DAVIES, Gideon j., WILLIAMS, Spencer j.. Combined inhibitor free-energy landscape and structural analysis reports on the mannosidase conformational coordinate. _Angewandte Chemie-International Edition_. 2014. Vol. 53, núm. 4, pàgs. 1087-1091. [consulta: 23 de gener de 2026]. ISSN: 1433-7851. [Disponible a: https://hdl.handle.net/2445/122754]

Exportar metadades

JSON - METS

Compartir registre