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A nucleotide-sensin...
A nucleotide-sensing oligomerization mechanism that controls NrdR-dependent transcription of ribonucleotide reductases
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- Rozman Grinberg, Inna (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Martínez-Carranza, Markel (author)
- Stockholms universitet,Stockholm University,Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Institutionen för biokemi och biofysik,Lund University, Sweden
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- Bimai, Ornella, 1991- (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Nouaïria, Ghada (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Shahid, Saher, 1987- (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Lundin, Daniel, 1965- (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Logan, Derek T (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Sjöberg, Britt-Marie (author)
- Stockholms universitet,Stockholm University,Institutionen för biokemi och biofysik
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- Stenmark, Pål (author)
- Stockholms universitet,Stockholm University,Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Institutionen för biokemi och biofysik,Lund University, Sweden
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(creator_code:org_t)
- 2022-05-16
- 2022
- English 10 s.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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https://doi.org/10.1...
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Abstract
Subject headings
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- Ribonucleotide 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- Adenosine Triphosphate/metabolism
- Cryoelectron Microscopy
- Gene Expression Regulation, Bacterial
- Nucleotides/chemistry
- Ribonucleotide Reductases/genetics
- Streptomyces coelicolor/metabolism
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Rozman Grinberg, ...
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Martínez-Carranz ...
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Bimai, Ornella, ...
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Nouaïria, Ghada
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Shahid, Saher, 1 ...
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Lundin, Daniel, ...
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Logan, Derek T
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Sjöberg, Britt-M ...
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Stenmark, Pål
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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Nature Communica ...
- By the university
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Lund University
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Stockholm University