7p3f
From Proteopedia
Streptomyces coelicolor dATP/ATP-loaded NrdR in complex with its cognate DNA
Structural highlights
FunctionNRDR_STRCO Negatively regulates transcription of nrdRJ (class II RNR genes) and nrdABS operon (class I RNR genes) by binding to NrdR-boxes which are proximal to or overlap with the promoter regions of class II and class Ia RNR operons, respectively.[1] [2] [3] Publication Abstract from PubMedRibonucleotide reductase (RNR) is an essential enzyme that catalyzes the synthesis of DNA building blocks in virtually all living cells. NrdR, an RNR-specific repressor, controls the transcription of RNR genes and, often, its own, in most bacteria and some archaea. NrdR senses the concentration of nucleotides through its ATP-cone, an evolutionarily mobile domain that also regulates the enzymatic activity of many RNRs, while a Zn-ribbon domain mediates binding to NrdR boxes upstream of and overlapping the transcription start site of RNR genes. Here, we combine biochemical and cryo-EM studies of NrdR from Streptomyces coelicolor to show, at atomic resolution, how NrdR binds to DNA. The suggested mechanism involves an initial dodecamer loaded with two ATP molecules that cannot bind to DNA. When dATP concentrations increase, an octamer forms that is loaded with one molecule each of dATP and ATP per monomer. A tetramer derived from this octamer then binds to DNA and represses transcription of RNR. In many bacteria - including well-known pathogens such as Mycobacterium tuberculosis - NrdR simultaneously controls multiple RNRs and hence DNA synthesis, making it an excellent target for novel antibiotics development. A nucleotide-sensing oligomerization mechanism that controls NrdR-dependent transcription of ribonucleotide reductases.,Rozman Grinberg I, Martinez-Carranza M, Bimai O, Nouairia G, Shahid S, Lundin D, Logan DT, Sjoberg BM, Stenmark P Nat Commun. 2022 May 16;13(1):2700. doi: 10.1038/s41467-022-30328-1. PMID:35577776[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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