Molecular Biology

Secondary Metabolites

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Science  20 Aug 2004:
Vol. 305, Issue 5687, pp. 1079-1081
DOI: 10.1126/science.305.5687.1079e

Bacteria need to be able to change gene expression rapidly when conditions change. A sudden decrease in amino acid nutrients will trigger the synthesis of guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a molecule that halts continued growth by blocking ribosomal RNA (rRNA) synthesis and that turns on the expression of amino acid biosynthetic genes. Paul et al. and Perederina et al. provide complementary evidence that the bacterial protein DksA binds to RNA polymerase (RNAP) and mediates the inhibitory effect of ppGpp by destabilizing the open RNAP-promoter complex and thus blocking initiation of transcription at rRNA promoters. DksA is structurally similar to GreA, which regulates the elongation phase of transcription. Both proteins possess a coiled-coil domain that appears to fit into the RNAP secondary channel, whose likely function is to allow nucleotides access to the active site. By accommodating a variety of transcriptional regulators, the secondary channel of RNAP may also facilitate bacterial adjustments to a broad range of environmental conditions, and the development of occluders of the secondary channel may prove therapeutically useful against harmful bacteria. — LDC

Cell 118, 311; 297 (2004)

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