7oj2
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Bacillus subtilis IMPDH in complex with Ap4A== | |
| + | <StructureSection load='7oj2' size='340' side='right'caption='[[7oj2]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7oj2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OJ2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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=7oj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oj2 OCA], [https://pdbe.org/7oj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oj2 RCSB], [https://www.ebi.ac.uk/pdbsum/7oj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oj2 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/IMDH_BACSU IMDH_BACSU]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_01964] | ||
| + | <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 7oj2" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bacillus subtilis subsp. subtilis str. 168]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bange G]] | ||
| + | [[Category: Giammarinaro PI]] | ||
Revision as of 06:52, 14 September 2022
Bacillus subtilis IMPDH in complex with Ap4A
| |||||||||||
