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Compounds with capa...
Compounds with capacity to quench the tyrosyl radical in Pseudomonas aeruginosa ribonucleotide reductase
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- Berggren, Gustav (author)
- Uppsala universitet,Molekylär biomimetik
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- Sahlin, Margareta (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden
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- Crona, Mikael (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden;Swedish Orphan Biovitrum AB, Stockholm, Sweden
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- Tholander, Fredrik (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden
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- Sjöberg, Britt-Marie (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden
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(creator_code:org_t)
- 2019-06-20
- 2019
- English.
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In: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 24:6, s. 841-848
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Abstract
Subject headings
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- Ribonucleotide reductase (RNR) has been extensively probed as a target enzyme in the search for selective antibiotics. Here we report on the mechanism of inhibition of nine compounds, serving as representative examples of three different inhibitor classes previously identified by us to efficiently inhibit RNR. The interaction between the inhibitors and Pseudomonas aeruginosa RNR was elucidated using a combination of electron paramagnetic resonance spectroscopy and thermal shift analysis. All nine inhibitors were found to efficiently quench the tyrosyl radical present in RNR, required for catalysis. Three different mechanisms of radical quenching were identified, and shown to depend on reduction potential of the assay solution and quaternary structure of the protein complex. These results form a good foundation for further development of P. aeruginosa selective antibiotics. Moreover, this study underscores the complex nature of RNR inhibition and the need for detailed spectroscopic studies to unravel the mechanism of RNR inhibitors.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Diferric-oxo center
- Radicals
- Inhibitors
- Ribonucleotide reductase
- Thermal shift analysis
- EPR
Publication and Content Type
- ref (subject category)
- art (subject category)
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