2WJZ: Crystal Structure Of (Hish) K181a Y138a Mutant Of Imidazoleglycerolphosphate Synthase (Hish Hisf) Which Displays Constitutive Glutaminase Activity

Nitrogen is incorporated into various metabolites by multifunctional glutamine amidotransferases via reactive ammonia generated by glutaminase hydrolysis of glutamine. Although this process is generally tightly regulated by subsequent synthase activity, little is known about how the glutaminase is inhibited in the absence of an activating signal. Here, we use imidazoleglycerolphosphate synthase as a model to investigate the mechanism of glutaminase regulation. A structure of the bienzyme-glutamine complex reveals that the glutaminase active site is in a catalysis-competent conformation but the ammonia pathway toward the synthase active site is blocked. Mutation of two residues blocking the pathway leads to a complete uncoupling of the two reactions and to a 2800-fold amplification of glutaminase activity. Our data advance the understanding of coupling enzymatic activities in glutamine amidotransferases and raise hypotheses of the underlying molecular mechanism.
PDB ID: 2WJZDownload
MMDB ID: 84285
PDB Deposition Date: 2009/6/2
Updated in MMDB: 2010/08
Experimental Method:
x-ray diffraction
Resolution: 2.601  Å
Source Organism:
Similar Structures:
Biological Unit for 2WJZ: dimeric; determined by author and by software (PISA)
Molecular Components in 2WJZ
Label Count Molecule
Proteins (2 molecules)
Imidazole Glycerol Phosphate Synthase Hisf(Gene symbol: TM1036)
Molecule annotation
Imidazole Glycerol Phosphate Synthase Subunit Hish(Gene symbol: hisH)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB