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==Light-Regulation of Imidazole Glycerol Phosphate Synthase by Interference with its Allosteric Machinery through Photo-Sensitive Unnatural Amino Acids== | ==Light-Regulation of Imidazole Glycerol Phosphate Synthase by Interference with its Allosteric Machinery through Photo-Sensitive Unnatural Amino Acids== | ||
<StructureSection load='6rtz' size='340' side='right'caption='[[6rtz]]' scene=''> | <StructureSection load='6rtz' size='340' side='right'caption='[[6rtz]], [[Resolution|resolution]] 2.87Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RTZ OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6rtz]] is a 2 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=6RTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RTZ FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.87Å</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=6rtz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rtz OCA], [https://pdbe.org/6rtz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rtz RCSB], [https://www.ebi.ac.uk/pdbsum/6rtz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rtz ProSAT]</span></td></tr> | |||
</table> | </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] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Imidazole glycerol phosphate synthase (ImGPS) is an allosteric bienzyme complex in which substrate binding to the synthase subunit HisF stimulates the glutaminase subunit HisH. To control this stimulation with light, we have incorporated the photo-responsive unnatural amino acids phenylalanine-4'-azobenzene (AzoF), o-nitropiperonyl-O-tyrosine (NPY), and methyl-o-nitropiperonyllysine (mNPK) at strategic positions of HisF. The light-mediated isomerization of AzoF at position 55 (fS55AzoF(E) <--> fS55AzoF(Z)) resulted in a reversible 10-fold regulation of HisH activity. The light-mediated decaging of NPY at position 39 (fY39NPY --> fY39) and of mNPK at position 99 (fK99mNPK --> fK99) led to a 4- to 6-fold increase of HisH activity. Molecular dynamics simulations explained how the unnatural amino acids interfere with the allosteric machinery of ImGPS and revealed additional aspects of HisH stimulation in wild-type ImGPS. Our findings show that unnatural amino acids can be used as a powerful tool for the spatiotemporal control of a central metabolic enzyme complex by light. | |||
Light Regulation of Enzyme Allostery through Photo-responsive Unnatural Amino Acids.,Kneuttinger AC, Straub K, Bittner P, Simeth NA, Bruckmann A, Busch F, Rajendran C, Hupfeld E, Wysocki VH, Horinek D, Konig B, Merkl R, Sterner R Cell Chem Biol. 2019 Nov 21;26(11):1501-1514.e9. doi:, 10.1016/j.chembiol.2019.08.006. Epub 2019 Sep 5. PMID:31495713<ref>PMID:31495713</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6rtz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[IGPS 3D structures|IGPS 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Thermotoga maritima]] | |||
[[Category: Kneuttinger A]] | [[Category: Kneuttinger A]] | ||
[[Category: Rajendran C]] | [[Category: Rajendran C]] | ||
[[Category: Sterner R]] | [[Category: Sterner R]] | ||