2WJZ

Crystal structure of (HisH) K181A Y138A mutant of imidazoleglycerolphosphate synthase (HisH HisF) which displays constitutive glutaminase activity

Summary for 2WJZ

• Entry DOI: 10.2210/pdb2wjz/pdb
• Related: 1GPW 1K9V 1KXJ 1THF 1VH7 2A0N 2W6R
• Descriptor: IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE HISF, IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE SUBUNIT HISH, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: lyase-transferase complex, amino-acid biosynthesis, ammonia channel, histidine biosynthesis, cyclase, glutaminase, lyase/transferase
• Biological source: THERMOTOGA MARITIMA; More
• Cellular location: Cytoplasm: Q9X0C6 Q9X0C8
• Total number of polymer chains: 6
• Total formula weight: 152487.63

Authors

Vega, M.C.,List, F.,Razeto, A.,Haeger, M.C.,Babinger, K.,Kuper, J.,Sterner, R.,Wilmanns, M. (deposition date: 2009-06-02, release date: 2010-08-25, Last modification date: 2023-12-13)

Primary citation

List, F.,Vega, M.C.,Razeto, A.,Hager, M.C.,Sterner, R.,Wilmanns, M.
Catalysis Uncoupling in a Glutamine Amidotransferase Bienzyme by Unblocking the Glutaminase Active Site.
Chem.Biol., 19:1589-, 2012

PubMed Abstract: 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.

PubMed: 23261602
DOI: 10.1016/J.CHEMBIOL.2012.10.012

Experimental method

X-RAY DIFFRACTION (2.601 Å)