Maryam Zare - Department of Biology, Payame Noor University, Avaj, Iran
Faranak Hadi - Department of Biology, Faculty of Science, Lorestan University, Khoramabad, Iran.
Zarrin Minuchehr - Industrial and Environmental Biotechnology Department, National Institute of Genetic Engineering & Biotechnology (NIGEB), Tehran, Iran.
Jafar Amani - Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Mammalian Δ-(1)-Pyrroline-5-carboxylate synthase (P5CS) enzyme catalyzes the coupled phosphorylation and reduction-conversion of glutamate to Δ-(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 ofproline, ornithine, citruline and arginine. A missense mutation, R84Q, which altersthe 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 includesthe 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.

Pyrroline-5-Carboxylate Synthase, Amino Acid Substitutions, Tertiary Structure Modeling