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7oj1
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Bacillus subtilis IMPDH in complex with Ap4A== | |
| + | <StructureSection load='7oj1' size='340' side='right'caption='[[7oj1]], [[Resolution|resolution]] 2.44Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7oj1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJ1 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B4P:BIS(ADENOSINE)-5-TETRAPHOSPHATE'>B4P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7oj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oj1 OCA], [https://pdbe.org/7oj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oj1 RCSB], [https://www.ebi.ac.uk/pdbsum/7oj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oj1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Diadenosine tetraphosphate (Ap4A) is a putative second messenger molecule that is conserved from bacteria to humans. Nevertheless, its physiological role and the underlying molecular mechanisms are poorly characterized. We investigated the molecular mechanism by which Ap4A regulates inosine-5'-monophosphate dehydrogenase (IMPDH, a key branching point enzyme for the biosynthesis of adenosine or guanosine nucleotides) in Bacillus subtilis. We solved the crystal structure of BsIMPDH bound to Ap4A at a resolution of 2.45 A to show that Ap4A binds to the interface between two IMPDH subunits, acting as the glue that switches active IMPDH tetramers into less active octamers. Guided by these insights, we engineered mutant strains of B. subtilis that bypass Ap4A-dependent IMPDH regulation without perturbing intracellular Ap4A pools themselves. We used metabolomics, which suggests that these mutants have a dysregulated purine, and in particular GTP, metabolome and phenotypic analysis, which shows increased sensitivity of B. subtilis IMPDH mutant strains to heat compared with wild-type strains. Our study identifies a central role for IMPDH in remodelling metabolism and heat resistance, and provides evidence that Ap4A can function as an alarmone. | ||
| - | + | Diadenosine tetraphosphate regulates biosynthesis of GTP in Bacillus subtilis.,Giammarinaro PI, Young MKM, Steinchen W, Mais CN, Hochberg G, Yang J, Stevenson DM, Amador-Noguez D, Paulus A, Wang JD, Bange G Nat Microbiol. 2022 Sep;7(9):1442-1452. doi: 10.1038/s41564-022-01193-x. Epub, 2022 Aug 11. PMID:35953658<ref>PMID:35953658</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7oj1" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bacillus subtilis]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bange G]] | ||
| + | [[Category: Giammarinaro PI]] | ||
Revision as of 06:52, 14 September 2022
Bacillus subtilis IMPDH in complex with Ap4A
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