Invasive fungal
opportunistic infections or
mycoses have been on the rise with increase in the number of immuno-compromised patients accounting for associated high morbidity and mortality rates. The antifungal drugs are not completely effective due to increased resistance and varied susceptibility of fungi. Hence, the functional diversification study of novel targets has to be carried out. The
enzyme glucosamine-6-phosphate synthase [EC 2.6.1.16], a novel
drug target, catalyzes the rate-limiting step of the fungal cell-wall biosynthetic pathway, comprising four conserved domains, two
glutaminase and
sugar-isomerising (SIS) domains with active site. The
amino acids within these domains tend to mutate simultaneously and exert mutual selective forces which might result in untoward fungal adaptations that are fixed through random genetic drift over time. The current study is an attempt to investigate such 'non-independent' coevolving residues which play critical functional and structural role in the
protein. Residues with Shannon entropy ≦1 (calculated by the
Protein Variability Server) were considered and subsequently, positional correlations were estimated by InterMap3D 1.3 server. It was observed that majority of coevolving pairs of first SIS domain involved interactions with hydrophobic
leucine and found to be spatially coupled in 3-dimensional structure of the
enzyme. The coevolving groups of Aspergillus niger and Rhizopus oryzae species might play a role in drug resistance. Such coevolutionary analysis is important for understanding the receptor-
ligand interactions and effective
drug designing.