MOLECULAR MODELING AND IN SILICO CHARACTERIZATION OF NITROGEN METABOLITE REPRESSOR NmrA OF OPPORTUNISTIC HUMAN PATHOGEN Aspergillus fumigatus

Abstract

The most prevalent airborne human pathogenic fungus Aspergillus fumigatus is ubiquitous in soil and like other ascomycotous fungi it can utilize a variety of nitrogen sources. Nitrogen metabolite repression (NMR) may induce virulence in A. fumigatus as in pathogenic fungi but the mechanism of regulation and its key components are not identified. The present study focuses on the molecular modeling and in silico characterization of the main player of this regulation, the NmrA of A. fumigatus. Physiochemical and structural characterization using various sequence and structure based predictors and quality assessment of the proposed two- and three-dimensional models were carried out. The characteristic motifs such as glycine-rich NAD(P)-binding motif (GxxGxxG) and altered active site motif (HxxxK) were located in NmrA along with DNA-binding residues (T11, R39, D40 and A45). The results obtained using bioinformatics tools indicated that the protein was hydrophilic in nature, stable in vitro and had very low disorder probability. Based on the quality score, the proposed secondary and tertiary structures were correct and extremely good to represent NmrA of A. fumigatus. Phylogenetic analysis signified its close relation with NMR regulatory protein of opportunistic human pathogens A. lentulus and A. novofumigatus.