RESUMEN
Ornithine decarboxylase (ODC) is an immediate precursor of polyamine biosynthesis in Serratia marcescens and a potential target for inhibition of its growth. We predicted the 3D structural conformation of ODC enzyme and validated it using MDS in our previous study. In this current study, the potential inhibitors of ODC were obtained by virtual screening of potential inhibitors from ZINC database and studied in depth for their different binding pose. Among the ten virtually screened inhibitors, Conessine exhibited the best binding with ODC and its inhibition property was studied further by MDS studies. The natural compound conessine is isolated from plant Holarrhena antidysenterica and it is studied against ODC of Serratia marcenses for its inhibitory potentials. This revealed unforeseen twisted position in root mean square fluctuation (RMSF) and ODC modelled conformation that influenced ligand binding. Both predicted model and ligand bound model were compared and found to be stable with Root Mean Square Deviation (RMSD) of approximately 7â¯nm and 0.25â¯nm to that of crystallographic structure over simulation time of 55â¯ns and 70â¯ns respectively. This work paves the way for future development of new drugs against nosocomial diseases caused by Serratia marcescens.
Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Simulación de Dinámica Molecular , Serratia marcescens/efectos de los fármacos , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/química , Sitios de Unión , Dominio Catalítico , Evaluación Preclínica de Medicamentos , Enlace de Hidrógeno , Ligandos , Conformación Molecular , Unión Proteica , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Relación Estructura-Actividad CuantitativaRESUMEN
Advances in the fields of genomic sciences have given rise to personalized medicine. This new paradigm draws upon a patient's genetic and metabolic makeup in order to tailor diagnostics and treatment. Personalized medicine holds remarkable promises to improve prevention and management of chronic diseases of global relevance, such as Type 2 diabetes mellitus (T2DM). This review article aims at summarizing the evidence from genome-based sciences on T2DM risk and management in different populations and in the Global Health context. Opinions from leading experts in the field were also included. Based on these findings, strengths and weaknesses of personalized approach to T2DM in a global context are delineated. Implications for future research and implementation on that subject are discussed.