Steve Ealick's Research Group

Thermotoga maritima PurLQS

PDB file:



Formylglycinamide ribonucleotide amidotransferase (FGAR-AT; encoded by the purL gene) catalyzes the ATP-dependent synthesis of formylglycinamidine ribonucleotide (FGAM) from formylglycinamide ribonucleotide (FGAR) and glutamine in the fourth step of the purine biosynthetic pathway. Two types of PurL have been detected. Large PurL (lgPurL) is found in eukaryotes and Gram-negative bacteria (such as Salmonella typhimurium PurL; StPurL) and consists of a single 140 kDa polypeptide chain. Small PurL (smPurL), is found in archaea and Gram-positive bacteria and consists of an approximately 80 kDa polypeptide chain. Small PurL (such as Themotoga maritima PurL (TmPurL)) requires two additional gene products, PurQ and PurS, for activity. PurQ is the glutaminase that provides ammonia from glutamine to be channeled to PurL. The TmPurLQS complex provides the first structure of a PurQ enzyme. In addition, comparisons of this complex with uncomplexed TmPurL and TmPurS as well as the StPurL structure enabled observation of protein movements that could be attributed to complex formation.  This permitted the description of a possible mechanism for communication between proteins within the complex and favored one of the two proposed locations for the ammonia channel (shown below).

Themotoga maritima PurQ has a classic glutaminase fold that consists of a nine stranded mixed b-sheet flanked by four a-helices, a pair of strands, and four 310 helices. In the complex, the TmPurQ active site is occupied by a glutamyl thioester intermediate covalently bound to Cys86.


Click the image to enlarge.

The TmPurLQS complex is composed of one molecule of TmPurL(shown in blue), one molecule of TmPurQ (above and in red at right) and one TmPurS dimer (similar to the Bacillus subtilis, BSPurS, dimer; in green at right).


Click the images to enlarge.

Two possible paths, labeled A and B, for the ammonia to move from PurQ to PurL are shown with light blue spheres. Superpositionof this structure with that of StPurL favors pathway B.

Click the image to enlarge.


Morar M, Hoskions AA, Stubbe J, and Ealick SE. Formylglycinamide Ribonucleotide Amidotransferase from Thermotoga maritima: Structural Insights into Complex Formation. Biochemistry 47:7816-7830 (2008).



Contacts Procedures Structures Projects Publications Lab Home Page Group Members