2wjz | pdb_00002wjz

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

spinqualitylabelsall models 2wjz, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wjz is a 6 chain structure with sequence from Atcc 43589 and Thermotoga maritima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PO4 Related: 2a0n, 1thf, 1kxj, 1gpw, 1k9v, 1vh7, 2w6r Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HIS6_THEMA] IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisF subunit catalyzes the cyclization activity that produces IGP and AICAR from PRFAR using the ammonia provided by the HisH subunit.[HAMAP-Rule:MF_01013] [HIS5_THEMA] IGPS catalyzes the conversion of PRFAR and glutamine to IGP, AICAR and glutamate. The HisH subunit provides the glutamine amidotransferase activity that produces the ammonia necessary to HisF for the synthesis of IGP and AICAR.[HAMAP-Rule:MF_00278] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Catalysis uncoupling in a glutamine amidotransferase bienzyme by unblocking the glutaminase active site.,List F, Vega MC, Razeto A, Hager MC, Sterner R, Wilmanns M Chem Biol. 2012 Dec 21;19(12):1589-99. doi: 10.1016/j.chembiol.2012.10.012. PMID:23261602 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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