Molecular Machines within us: The Glutamate Synthase

Glutamate Synthases are key enzymes in the early stages of the assimilation of ammonia in bacteria, yeast, and plants. Azospirillum brasilense glutamate synthase (GltS) is a complex iron-sulfur flavoprotein that catalyzes the reductive transfer of L-glutamine amide group to the (C2) carbon of 2-oxoglutarate(2OG) yielding two molecules of L-glutamate and whose function requires the transfer of ammonia and electrons among distinct catalytic sites. The NADPH-dependent Glutamate Synthase comprises of two subunits: alpha e beta. The α-subunit structure is composed of the following domains:

  • Amidotransferase domain (1-422)
  • Central domain (423-779)
  • FMN binding domain (780-1203)
  • C-terminal β-domain (1204-1432)



To obtain information on the mechanism of channel opening and ammonia tunneling, we undertook MD study of GltS in solution. Two 4 ns MD simulations of GltS in the substrate-free oxidized state and in the complex with its natural substrates L-glutamine and 2-oxoglutarate, reduced state. The results showed that in presence of the substrates the tunnel opens up to a radius of about 0.4 nm thus confirming the hypotheses path for the ammonia diffusion. It is interesting to note that in the substrate-free enzyme the tunnel opening is not observed. Furthermore, a cooperative domain closure motion upon the L-gln binding has been observed.

  1. M. Coiro, A. Di Nola, M. A. Vanoni, M. Aschi, A. Coda, D. Roccatano. Molecular dynamics simulation of interaction between the complex iron-sulfur flavoprotein glutamate synthase and its substrates. Prot. Sci., 13, 2979-2991 (2004).


About Danilo Roccatano

I have a Doctorate in chemistry at the University of Roma “La Sapienza”. I led educational and research activities at different universities in Italy, The Netherlands, Germany and now in the UK. I am fascinated by the study of nature with theoretical models and computational. For years, my scientific research is focused on the study of molecular systems of biological interest using the technique of Molecular Dynamics simulation. I have developed a server (the link is in one of my post) for statistical analysis at the amino acid level of the effect of random mutations induced by random mutagenesis methods. I am also very active in the didactic activity in physical chemistry, computational chemistry, and molecular modeling. I have several other interests and hobbies as video/photography, robotics, computer vision, electronics, programming, microscopy, entomology, recreational mathematics and computational linguistics.
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