7rmw

Crystal structure of B. subtilis PurR bound to ppGpp

spinqualitylabelsall models 7rmw, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rmw is a 6 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.45Å Ligands: G4P Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PURR_BACSU Controls the transcription of the pur operon for purine biosynthetic genes, binds to the control region of the operon. DNA binding is inhibited by 5-phosphoribosyl 1-pyrophosphate. Publication Abstract from PubMed The nucleotide messenger (p)ppGpp allows bacteria to adapt to fluctuating environments by reprogramming the transcriptome. Despite its well-recognized role in gene regulation, (p)ppGpp is only known to directly affect transcription in Proteobacteria by binding to the RNA polymerase. Here, we reveal a different mechanism of gene regulation by (p)ppGpp in Firmicutes: (p)ppGpp directly binds to the transcription factor PurR to downregulate purine biosynthesis gene expression upon amino acid starvation. We first identified PurR as a receptor of (p)ppGpp in Bacillus anthracis. A co-structure with Bacillus subtilis PurR reveals that (p)ppGpp binds to a PurR pocket reminiscent of the active site of phosphoribosyltransferase enzymes that has been repurposed to serve a purely regulatory role, where the effectors (p)ppGpp and PRPP compete to allosterically control transcription. PRPP inhibits PurR DNA binding to induce transcription of purine synthesis genes, whereas (p)ppGpp antagonizes PRPP to enhance PurR DNA binding and repress transcription. A (p)ppGpp-refractory purR mutant in B. subtilis fails to downregulate purine synthesis genes upon amino acid starvation. Our work establishes the precedent of (p)ppGpp as an effector of a classical transcription repressor and reveals the key function of (p)ppGpp in regulating nucleotide synthesis through gene regulation, from soil bacteria to pathogens. The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.,Anderson BW, Schumacher MA, Yang J, Turdiev A, Turdiev H, Schroeder JW, He Q, Lee VT, Brennan RG, Wang JD Nucleic Acids Res. 2021 Dec 30. pii: 6489957. doi: 10.1093/nar/gkab1281. PMID:34967415 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Purine repressor

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