6vwp

Crystal structure of E. coli guanosine kinase in complex with ppGpp

spinqualitylabelsall models 6vwp, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vwp is a 8 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.45Å Ligands: G4P, GMP, K, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function INGK_ECOLI Publication Abstract from PubMed (p)ppGpp is a nucleotide messenger universally produced in bacteria following nutrient starvation. In E. coli, ppGpp inhibits purine nucleotide synthesis by targeting several different enzymes, but the physiological significance of their inhibition is unknown. Here, we report the structural basis of inhibition for one target, Gsk, the inosine-guanosine kinase. Gsk creates an unprecedented, allosteric binding pocket for ppGpp by restructuring terminal sequences, which restrains conformational dynamics necessary for catalysis. Guided by this structure, we generated a chromosomal mutation that abolishes Gsk regulation by ppGpp. This mutant strain accumulates abnormally high levels of purine nucleotides following amino-acid starvation, compromising cellular fitness. We demonstrate that this unrestricted increase in purine nucleotides is detrimental because it severely depletes pRpp and essential, pRpp-derived metabolites, including UTP, histidine, and tryptophan. Thus, our results reveal the significance of ppGpp's regulation of purine nucleotide synthesis and a critical mechanism by which E. coli coordinates biosynthetic processes during starvation. ppGpp Coordinates Nucleotide and Amino-Acid Synthesis in E. coli During Starvation.,Wang B, Grant RA, Laub MT Mol Cell. 2020 Oct 1;80(1):29-42.e10. doi: 10.1016/j.molcel.2020.08.005. Epub, 2020 Aug 27. PMID:32857952 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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