Seeing Two Spots

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Science  14 May 2004:
Vol. 304, Issue 5673, pp. 931
DOI: 10.1126/science.304.5673.931c

More than a few decades ago, when paper electrophoresis was in vogue, two unusual nucleotides (ppGpp and pppGpp) were identified and called magic spots I and II. These spots—collectively called (p)ppGpp—appeared when Escherichia coli were starved of amino acids and ran into problems making proteins. Subsequent work established that the ribosome-associated enzyme RelA synthesized (p)ppGpp when uncharged transfer RNAs (depleted of their cognate amino acids) entered the ribosome and that (p)ppGpp served as a pleiotropic regulator of gene expression.

Hogg et al. describe structural and biochemical studies on two conformations of a Rel/Spo homolog from Streptococcus; Spo degrades (p)ppGpp and has sequence similarity to Rel. They find two catalytic sites, one for (p)ppGpp synthesis and one for hydrolysis, that are active in mutually exclusive fashion. Artsimovitch et al. observe two orientations of (p)ppGpp binding to the six-subunit RNA polymerase from Thermus thermophilus. They suggest that the differential impact of these orientations on binding of Mg2+, nucleotides, and the nontemplate DNA strand may account for the inhibitory and stimulatory effects of (p)ppGpp on transcription. —GJC

Cell 117, 57; 299 (2004).

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