Mostrar el registro sencillo del ítem

dc.contributor.authorArafet, Kemel
dc.contributor.authorFerrer Castillo, Silvia
dc.contributor.authorMoliner, Vicent
dc.identifier.citationARAFET, Kemel; FERRER, Silvia; MOLINER, Vicent. Computational Study of the Catalytic Mechanism of the Cruzain Cysteine Protease. ACS Catalysis, 2017, vol. 7, no 2, p. 1207-1215.ca_CA
dc.description.abstractCysteine proteases of the papain family are involved in many diseases, making them attractive targets for developing drugs. In this paper, different catalytic mechanisms of cruzain cysteine protease have been studied on the basis of molecular dynamics simulations within hybrid quantum mechanics/molecular mechanics potentials. The obtained free energy surfaces have allowed characterizing every single step along the mechanisms. The results confirm that the full process can be divided into an acylation and a deacylation stage, but important differences with respect to previous studies can be deduced from our calculations. Thus, our calculations suggest that the acylation stage takes place in a stepwise mechanism where a proton from a conserved His159 is transferred first to the N1 atom of the peptide and, after a transient intermediate is located, the Cys25 attacks the carbonyl carbon atom. The stabilization of the activated Cys25 is achieved by an effect of the local environment through interactions with residues Trp26, Gly160, and His159, rather than by a less complex Cys25S–/His159H+ ion pair. In contrast, the deacylation stage, which was proposed to occur via a general base-catalyzed reaction whereby His159 activates a water molecule that attacks the peptide, would take place through a concerted mechanism. In this stage, the role of some residues of the active site, such as Gln19, Asn175, and Trp181, appears to also be crucial. Interestingly, the local environment of His159 would be modulating its pKa value to act as an acid in the acylation stage and as a base in the following deacylation stage.ca_CA
dc.description.sponsorShipK.A. thanks the Spanish Ministerio de Economía y Competitividad for a predoctoral contract. The authors acknowledge computational resources from the Servei d’Informàtica of Universitat Jaume I.
dc.format.extent9 p.ca_CA
dc.publisherAmerican Chemical Societyca_CA
dc.relation.isPartOfACS Catalysis, 2017, vol. 7, no 2
dc.rightsCopyright © American Chemical Societyca_CA
dc.subjectcatalytic mechanismca_CA
dc.subjectcysteine proteasesca_CA
dc.subjectmolecular dynamicsca_CA
dc.titleComputational Study of the Catalytic Mechanism of the Cruzain Cysteine Proteaseca_CA
dc.relation.projectIDSpanish Ministerio de Economia y Competitividad / CTQ2015-66223-C2-1-P; Universitat Jaume I / P1.1B2014-26; Generalitat Valenciana / PROMETEOII/2014/022ca_CA

Ficheros en el ítem


No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Ministerio Este proyecto ha recibido una ayuda de la Dirección General del Libro, Archivos y Bibliotecas del Ministerio de Cultura.
Metadatos sujetos a :Public Domain | Información y | Centro de seguridad y privacidad | Nota legal
Universitat Jaume I - Av. de Vicent Sos Baynat, s/n 12071 Castelló de la Plana, España - Tel.: +34 964 72 87 61 Fax: +34 964 72 87 78