Applied Microbiology and Biotechnology

, Volume 98, Issue 23, pp 9545–9560 | Cite as

Squaring up to DNA: pentapeptide repeat proteins and DNA mimicry

  • Shama Shah
  • Jonathan G. Heddle


Pentapeptide repeats are a class of proteins characterized by the presence of multiple repeating sequences five amino acids in length. The sequences fold into a right-handed β-helix with a roughly square-shaped cross section. Pentapeptide repeat proteins include a number of examples which are thought to function as structural mimics of DNA and act to competitively bind to the type II topoisomerase DNA gyrase, an important antibacterial target. DNA gyrase-targeting pentapeptide repeat proteins can both inhibit DNA gyrase—a potentially useful therapeutic property—and contribute to resistance to quinolone antibacterials (by acting to prevent them forming a lethal complex with the DNA and enzyme). Pentapeptide repeat proteins are therefore of wide interest not only because of their unusual structure, function, and potential as an antibacterial target, but also because knowledge of their mechanism of action may lead to both a greater understanding of the details of DNA gyrase function as well as being a useful template for the design of new DNA gyrase inhibitors. However, many puzzling aspects as to how these DNA mimics function and indeed even their ability to act as DNA mimics itself remains open to question. This review summarizes the current state of knowledge regarding pentapeptide repeat proteins, focusing on those that are thought to mimic DNA, and speculates on potential structure-function relationships which may account for their differing specificities.


DNA gyrase Topoisomerase Pentapeptide repeat proteins MfpA Qnr DNA mimicry 



We thank Anthony Maxwell, James Berger, Ting-Yu Lin, and Soshichiro Nagano for critical reading of the manuscript, Soshichiro Nagano for useful discussions and assistance with sequence alignments, and Ting-Yu Lin for elements of Fig. 4. SS and JGH were funded by RIKEN Initiative Research Funding awarded to JGH, and SS was funded as a RIKEN Junior Research Associate.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Heddle Initiative Research UnitRIKENWakoJapan
  2. 2.Department of Life Science and Medical BioscienceWaseda UniversityShinjukuJapan

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