GARS Human, sf9

GARS is an (alpha)2 dimer, meaning it consists of two identical subunits. The enzyme operates by forming an aminoacyl-adenylate intermediate (Gly-AMP) before transferring the glycine to the tRNA. This ATP-dependent reaction is vital for the accurate translation of the genetic code .

In addition to its primary function, GARS also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule involved in various cell regulation pathways. This secondary function highlights the enzyme’s versatility and importance in cellular processes .

The human recombinant form of GARS is often produced using the sf9 insect cell expression system. This system is favored for its ability to produce glycosylated proteins, which are essential for maintaining the enzyme’s functionality and stability. The recombinant GARS produced in sf9 cells is typically tagged with a His-tag at the N-terminus to facilitate purification through chromatographic techniques .

GARS has been identified as a target of autoantibodies in autoimmune diseases such as polymyositis and dermatomyositis. These conditions are characterized by muscle inflammation and weakness, and the presence of autoantibodies against GARS suggests its involvement in the pathogenesis of these diseases .

Moreover, mutations in the GARS1 gene, which encodes GARS, have been linked to neurological disorders such as Charcot-Marie-Tooth disease type 2D (CMT2D) and distal hereditary motor neuropathy type V (HMN5). These genetic disorders are characterized by progressive muscle weakness and atrophy, further underscoring the enzyme’s critical role in maintaining neuromuscular health .

Recombinant GARS is supplied in a buffer solution containing HEPES, NaCl, and glycerol to ensure its stability. It should be stored at 4°C for short-term use (2-4 weeks) or frozen at -20°C for longer periods. It is important to avoid multiple freeze-thaw cycles to maintain the enzyme’s activity .