Document Type: Original Article
Department of Biology, Payame Noor University, Avaj, Iran
Department of Biology, Faculty of Science, Lorestan University, Khoramabad, Iran
Industrial and Environmental Biotechnology Department, National Institute of Genetic Engineering & Biotechnology (NIGEB), Tehran, Iran
Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Department of Plant Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
Mammalian ∆-(1)-Pyrroline-5-carboxylate synthase (P5CS) enzyme catalyzes the coupled phosphorylation and reduction-conversion of glutamate to ∆-(1)-pyrroline-5-carboxylate (P5C), a critical step in the proline, ornithine, citrulline and arginine biosynthesis. In plants and mammals, P5CS consists of two separate enzymatic domains: N-terminal γ-glutamyl kinase (γ-GK) and C-terminal γ-glutamyl phosphate reductase (γ–GPR). Hyperammonemia has been reported as a new inborn disorder, with a range of clinical symptoms which is associated with a reduced synthesis of proline, ornithine, citruline and arginine. A missense mutation, R84Q, which alters the conserved residue in γ-GK domain, is responsible for this disorder. In this study using in-silico approaches as a new bioinformatics method, sequence analysis was performed and the tertiary structure of γ-GK domain of human P5CS, which includes the R84Q missense mutation, was predicted and the mutation effects on structural and functional features of P5CS enzyme were analyzed. Our analysis showed that this substitution has an affect on the molecular surface accessibility and total energy of the modeled structure. We conclude that this mutation results in a reduced activity of P5CS enzyme and an impaired synthesis of these amino acids.