6gfm
From Proteopedia
Crystal structure of the Escherichia coli nucleosidase PpnN (pppGpp-form)
Structural highlights
FunctionPPNN_ECOLI Catalyzes the hydrolysis of the N-glycosidic bond of diverse pyrimidine and purine nucleotide 5'-monophosphates, to form ribose 5-phosphate and the corresponding free base. Can use AMP, GMP, IMP, CMP, dTMP and UMP as substrates. Cannot catalyze the reverse reactions. Is required for optimal growth in glucose minimal medium, possibly because it contributes to nucleoside pool homeostasis by degrading excess nucleotides and feeding back the ribose moiety to catabolism.[1] Publication Abstract from PubMedThe stringent response alarmones pppGpp and ppGpp are essential for rapid adaption of bacterial physiology to changes in the environment. In Escherichia coli, the nucleosidase PpnN (YgdH) regulates purine homeostasis by cleaving nucleoside monophosphates and specifically binds (p)ppGpp. Here, we show that (p)ppGpp stimulates the catalytic activity of PpnN both in vitro and in vivo causing accumulation of several types of nucleobases during stress. The structure of PpnN reveals a tetramer with allosteric (p)ppGpp binding sites located between subunits. pppGpp binding triggers a large conformational change that shifts the two terminal domains to expose the active site, providing a structural rationale for the stimulatory effect. We find that PpnN increases fitness and adjusts cellular tolerance to antibiotics and propose a model in which nucleotide levels can rapidly be adjusted during stress by simultaneous inhibition of biosynthesis and stimulation of degradation, thus achieving a balanced physiological response to constantly changing environments. (p)ppGpp Regulates a Bacterial Nucleosidase by an Allosteric Two-Domain Switch.,Zhang YE, Baerentsen RL, Fuhrer T, Sauer U, Gerdes K, Brodersen DE Mol Cell. 2019 Apr 16. pii: S1097-2765(19)30260-6. doi:, 10.1016/j.molcel.2019.03.035. PMID:31023582[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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