Isolation and Structure Elucidation of a New Indole Metabolite from Aspergillus ruber |
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| Authors: | Hiromichi Nagasawa Akira Isogai Katsutoshi Ikeda Shouhachi Sato Shigeo Murakoshi Akinori Suzuki |
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| Institution: | 1. Department of Agricultural Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo;2. Kanagawa Prefectural Livestock Experiment Station, Ebina-shi, Kanagawa-ken;3. Ebina-shi, Kanagawa-kenKanagawa Prefectural Institute for Sericultural Science, Ebina-shi, Kanagawa-ken |
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| Abstract: | A bacterial two-component signal transduction system, WalK/WalR, is essential to the cell viability of Gram-positive bacteria and is therefore a potential target for the development of a new class of antibiotics. We have solved the X-ray crystal structure of the DNA-binding domain of the response regulator WalR (WalRc) from a Gram-positive pathogen Staphylococcus aureus, currently causing serious problems in public health through the acquisition of multi-drug resistance. The structure contains a winged helix-turn-helix motif and closely resembles those of WalRs of Bacillus subtilis and Enterococcus faecalis, and also that of PhoB of Escherichia coli. Gel mobility shift assays with mutant WalRs revealed specific interactions of WalR with the target DNA, as elaborated by in silico modeling of the WalRc-DNA complex. |
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| Keywords: | antibiotics drug design response regulator (RR) two-component signal transduction system (TCS) X-ray crystallography |
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