Distinct mechanisms for DNA cleavage by myoglobin with a designed heme active center

Journal of Inorganic Biochemistry
Yuan ZhaoYing-Wu Lin

Abstract

Heme proteins perform diverse biological functions, of which myoglobin (Mb) is a representative protein. In this study, the O2 carrier Mb was shown to cleave double stranded DNA upon aerobic dithiothreitol-induced reduction, which is fine-tuned by an additional distal histidine, His29 or His43, engineered in the heme active center. Spectroscopic (UV-vis and EPR) and inhibition studies suggested that free radicals including singlet oxygen and hydroxyl radical are responsible for efficient DNA cleavage via an oxidative cleavage mechanism. On the other hand, L29E Mb, with a distinct heme active center involving three water molecules in the met form, was found to exhibit an excellent DNA cleavage activity that was not depending on O2. Inhibition and ligation studies demonstrated for the first time that L29E Mb cleaves double stranded DNA into both the nicked circular and linear forms via a hydrolytic cleavage mechanism, which resembles native endonucleases. This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can...Continue Reading

References

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Dec 17, 2014·Chemical Communications : Chem Comm·Gopeekrishnan Sreenilayam, Rudi Fasan

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Citations

Jun 7, 2019·Acta Biochimica Et Biophysica Sinica·Xiaodong CuiZhuanhua Wang
Dec 9, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Shun Hirota, Ying-Wu Lin

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