Article
Update and elucidation of plasmodium kinomes: prioritization of kinases as potential drug targets for malaria
Registro en:
BASTOS, Borba, Joyce Villa Verde et al. Update and elucidation of plasmodium kinomes: prioritization of kinases as potential drug targets for malaria. Computational and Structural Biotechnology Journal, v. 20, p. 1-10, 2022.
2001-0370
10.1016/j.csbj.2022.07.003
Autor
Borba, Joyce Villa Verde Bastos
Silva, Arthur de Carvalho e
Nascimento, Marília Nunes do
Ferreira, Letícia Tiburcio
Rimoldi, Aline
Starling, Luísa
Ramos, Pablo Ivan Pereira
Costa, Fabio Trindade Maranhão
Andrade, Carolina Horta
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
Fundação de Amparo à Pesquisa do Estado de Goiás (FAPEG).
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Malaria is a tropical disease caused by Plasmodium spp. and transmitted by the bite of infected Anopheles mosquitoes. Protein kinases (PKs) play key roles in the life cycle of the etiological agent of malaria, turning these proteins attractive targets for antimalarial drug discovery campaigns. As part of an effort to understand parasite signaling functions, we report the results of a bioinformatics pipeline analysis of PKs of eight Plasmodium species. To date, no P. malariae and P. ovale kinome assemble has been conducted. We classified, curated and annotated predicted kinases to update P. falciparum, P. vivax, P. yoelii, P. berghei, P. chabaudi, and P. knowlesi kinomes published to date, as well as report for the first time the kinomes of P. malariae and P. ovale. Overall, from 76 to 97 PKs were identified among all Plasmodium spp. kinomes. Most of the kinases were assigned to seven of nine major kinase groups: AGC, CAMK, CMGC, CK1, STE, TKL, OTHER; and the Plasmodium-specific group FIKK. About 30% of kinases have been deeply classified into group, family and subfamily levels and only about 10% remained unclassified. Furthermore, updating and comparing the kinomes of P. vivax and P. falciparum allowed for the prioritization and selection of kinases as potential drug targets that could be explored for discovering new drugs against malaria. This integrated approach resulted in the selection of 37 protein kinases as potential targets and the identification of investigational compounds with moderate in vitro activity against asexual P. falciparum (3D7 and Dd2 strains) stages that could serve as starting points for the search of potent antimalarial leads in the future.
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Identificación y caracterización de la proteína del cuello de las roptrias 5 (RON5) en Plasmodium falciparum y determinación de las regiones de unión a glóbulos rojos humanos
Patarroyo Gutiérrez, Manuel Alfonso (Universidad de La Sabana, 2014-03-14)In this research, advanced control strategies were designed under the Active Disturbance Rejection Control (ADRC) approach to increase the biomass production in microalgae cultures. For the above, from a control frame of ... -
High plasmodium malariae prevalence in an endemic area of the colombian amazon region
Camargo-Ayala, Paola Andrea; Cubides, Juan Ricardo; Niño, Carlos Hernando; Camargo, Milena; Rodríguez-Celis, Carlos Arturo; Quiñones, Teódulo; Sánchez-Suárez, Lizeth; Patarroyo, Manuel Elkin; Patarroyo, Manuel A. (2016) -
Resistencia de Plasmodium falciparum A Tres Fármacos Antimaláricos En Turbo (Antioquia, Colombia), 1998
Blair Trujillo, Silvia; Lacharme Lora, Leidy; Carmona Fonseca, Jaime; Tobón Castaño, Alberto