Glutamine synthase structure

The structure of glutamine synthase from Salmonella typhimurium. The enzyme consists of twelve identical subunits arranged like a hexagonal prism, (a) View down the sixfold axis of symmetry. The top ring of monomers are alternately colored light and dark blue and the bottom ring of monomers light and dark red. The active sites of each monomer are marked by pairs of Mn"+ ions (white spheres). 

Molecules with structures as diverse as carbamoyl-phosphate, tryptophan, and cytidine triphosphate are feedback inhibitors of the E. coli glutamine synthase. The feedback inhibition is cumulative, with each metabolite exerting a partial inhibition on the enzyme. Why would complete inhibition of the glutamine synthase by a single metabolite be metaboli-cally unsound ... 

Given the structural diversity of the compounds that feedback-inhibit glutamine synthase, would you predict that they interact at a common regulatory site ... 

The figure shows the steps catalyzed by glutamine synthase and the structural similarity between glutamic acid, MSO, and glufosinate. 

Structural analysis revealed a folding pattern (Class X) related to that of a nucleotidyltransferase superfamily that includes enzymes such as terminal deoxy-nucleotidyltransferase (Chapter 12) and the glutamine synthase adenylytransferase (Fig. 24-7). " However, its active site (Fig. 27-13) is similar to that of other DNA polymerases. 

In the tryptophan branch (Fig. 22-17), chorismate is converted to anthranilate in a reaction in which glutamine donates the nitrogen that will become part of the indole ring. Anthranilate then condenses with PRPP. The indole ring of tryptophan is derived from the ring carbons and amino group of anthranilate plus two carbons derived from PRPP. The final reaction in the sequence is catalyzed by tryptophan synthase. This enzyme has an a2/32 subunit structure and can be dissociated into two a subunits and a /32 subunit that catalyze different parts of the overall reaction ... 

As stated above, the only other known route for the biosynthesis of PLP is dependent upon R5P, G3P, and glutamine, and is catalyzed by a single enzyme complex. The PLP synthase holoenzyme complex consists of 12 synthase (Pdxl) subunits and 12 glutaminase (Pdx2) subunits that form into a cogwheel-type structure (Figure yj 36.39,41,42,59 subunits decorate the exterior of this cogwheel and catalyze the hydrolysis of... 

Figure 11 The structure of carbamoyl phosphate synthase, showing in gray mesh the tunnel that transfers ammonia released from glutamine by the small subunit (blue) to an active site in the N-terminal domain of the large subunit (green), where it reacts with carbonate and ATP to form carbamate. The carbamate then travels through the tunnel to a third active site in the C-terminal domain of the large subunit (purple), where it is phosphorylated by ATP to form carbamoyl phosphate. Reproduced with permission from A. Weeks L. Lund F. M. Raushel, Cuir. Opin. Chem. Biol. 2006, 10, 465-472.

GFAT is unusual among amidotransferases in being unable to use ammonia as an alternate nitrogen source under in vitro conditions, precluding any direct assessment of the ability of glutamine to suppress ammonia-dependent synthase activity. The process of ammonia translocation has therefore been studied by steered MD simulations on a model of the active enzyme built from the crystal structure of the DON-modified form of... 

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