View source for 2wjz


==Crystal structure of (HisH) K181A Y138A mutant of imidazoleglycerolphosphate synthase (HisH HisF) which displays constitutive glutaminase activity==
<StructureSection load='2wjz' size='340' side='right'caption='[[2wjz]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wjz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WJZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.601&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wjz OCA], [https://pdbe.org/2wjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wjz RCSB], [https://www.ebi.ac.uk/pdbsum/2wjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wjz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HIS6_THEMA 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]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wj/2wjz_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wjz ConSurf].
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== 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<ref>PMID:23261602</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wjz" style="background-color:#fffaf0;"></div>

==See Also==
*[[IGPS 3D structures|IGPS 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermotoga maritima]]
[[Category: Babinger K]]
[[Category: Haeger MC]]
[[Category: Kuper J]]
[[Category: List F]]
[[Category: Razeto A]]
[[Category: Sterner R]]
[[Category: Vega MC]]
[[Category: Wilmanns M]]