The Natural Product Cyclomarin Kills Mycobacterium Tuberculosis by Targeting the ClpC1 Subunit of the Caseinolytic Protease (pages 5889–5891)
Dr. Esther K. Schmitt, Meliana Riwanto, Dr. Vasan Sambandamurthy, Dr. Silvio Roggo, Charlotte Miault, Christian Zwingelstein, Dr. Philipp Krastel, Dr. Christian Noble, Dr. David Beer, Srinivasa P. S. Rao, Melvin Au, Pornwaratt Niyomrattanakit, Viviam Lim, Dr. Jun Zheng, Dr. Douglas Jeffery, Dr. Kevin Pethe and Dr. Luis R. Camacho
Article first published online: 11 MAY 2011 | DOI: 10.1002/anie.201101740
Target practice: The target of the antibiotic cyclomarin A was identified in Mycobacterium. Cyclomarin A (see structure) binds the regulatory subunit of the Clp protease complex with high affinity resulting in elevated proteolysis and cell death. The property of cyclomarin to kill both growing and nonreplicating mycobacteria makes the Clp protease a promising target for antitubercular drug discovery.