6VWP

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

Summary for 6VWP

• Entry DOI: 10.2210/pdb6vwp/pdb
• Descriptor: Inosine-guanosine kinase, GUANOSINE-5',3'-TETRAPHOSPHATE, GUANOSINE, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Escherichia coli (strain K12)
• Total number of polymer chains: 8
• Total formula weight: 400275.66

Authors

Wang, B.,Grant, R.A.,Laub, M.T. (deposition date: 2020-02-20, release date: 2020-10-07, Last modification date: 2023-10-11)

Primary citation

Wang, B.,Grant, R.A.,Laub, M.T.
ppGpp Coordinates Nucleotide and Amino-Acid Synthesis in E. coli During Starvation.
Mol.Cell, 80:29-, 2020

PubMed Abstract: (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.

PubMed: 32857952
DOI: 10.1016/j.molcel.2020.08.005

Experimental method

X-RAY DIFFRACTION (3.45 Å)