Chemical Biology Approaches Reveal Conserved Features of a C‐Terminal Processing PDZ Protease

作者: Juliane Weski , Michael Meltzer , Lina Spaan , Timon Mönig , Julian Oeljeklaus

DOI: 10.1002/CBIC.201100643

关键词:

摘要: Several proteases like the high temperature requirement A (HtrA) protein family containing internal or C-terminal PDZ domains play key roles in quality control cell envelope of Gram-negative bacteria. While several HtrA have been extensively characterized, many features processing such as tail-specific protease (Tsp) are still unknown. To fully understand these cellular systems, individual need to be targeted by specific peptides acting activators inhibitors. Here, we describe identification and design potent inhibitors Tsp. Suitable synthetic substrates Tsp were identified served a basis for generation boronic acid-based peptide In addition, proteomic screen E. coli proteins using library was performed identify capable amplifying Tsp's proteolytic activity. The implications findings regulation future mechanistic studies discussed.

参考文章(47)
Jean-Luc Imler, Philippe Bulet, Antimicrobial peptides in Drosophila: structures, activities and gene regulation. Chemical immunology and allergy. ,vol. 86, pp. 1- 21 ,(2005) , 10.1159/000086648
Der-Ing Liao, Bruce A. Diner, Jin Qian, Dexter A. Chisholm, Douglas B. Jordan, Crystal structures of the photosystem II D1 C-terminal processing protease. Nature Structural & Molecular Biology. ,vol. 7, pp. 749- 753 ,(2000) , 10.1038/78973
A Seoane, A Sabbaj, L M McMurry, S B Levy, Multiple antibiotic susceptibility associated with inactivation of the prc gene. Journal of Bacteriology. ,vol. 174, pp. 7844- 7847 ,(1992) , 10.1128/JB.174.23.7844-7847.1992
Corinna Wilken, Karina Kitzing, Robert Kurzbauer, Michael Ehrmann, Tim Clausen, Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease. Cell. ,vol. 117, pp. 483- 494 ,(2004) , 10.1016/S0092-8674(04)00454-4
Linda Truebestein, Annette Tennstaedt, Timon Mönig, Tobias Krojer, Flavia Canellas, Markus Kaiser, Tim Clausen, Michael Ehrmann, Substrate-induced remodeling of the active site regulates human HTRA1 activity Nature Structural & Molecular Biology. ,vol. 18, pp. 386- 388 ,(2011) , 10.1038/NSMB.2013
David A. Rasko, Vanessa Sperandio, Anti-virulence strategies to combat bacteria-mediated disease Nature Reviews Drug Discovery. ,vol. 9, pp. 117- 128 ,(2010) , 10.1038/NRD3013
Kenneth C. Keiler, Robert T. Sauer, Sequence Determinants of C-terminal Substrate Recognition by the Tsp Protease Journal of Biological Chemistry. ,vol. 271, pp. 2589- 2593 ,(1996) , 10.1074/JBC.271.5.2589