In-silico structural investigation of Neisseria meningitidis (MC58) glutamate dehydrogenase

Abstract

Neisseria meningitidisis a commensalpathogen responsible for causing septicemia and meningitis worldwide. It has a mortality rate of 10% while the survivors demonstrate a high rate of sequelaecase. The discovery of specific and effective therapeutics is necessary to subdue this lethal infection. Glutamate dehydrogenase is considereda crucial drug target as it is a fundamental enzyme in the metabolic pathway of Neisseria. It catalyzes the reversible reaction of 2-oxoglutarate into glutamate. During the present studies, the three-dimensional model of N. meningitidisNADP-dependent glutamate dehydrogenase enzyme (NMB1710 gene product) was constructedusing the crystal structure of Corynebacterium glutamicum glutamate dehydrogenase complexed with 2-iminoglutarate and NADP+ as a template using MODELLER software. According to the stereochemical analysis and energy profiling, the modeled structure was found to be valid. The model was constructed in monomeric form, comprising of two core domains including catalytic and nucleotide-binding domain with a characteristic Rossmann fold. The catalytically significant residues showed strict conservation with that of the template. Structural elucidation of the glutamate dehydrogenase ezyme will be helpful for protein-ligand docking studies in order to identify certain potent drugs against this deadly pathogen.