کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2401865 1102377 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterizing septum inhibition in Mycobacterium tuberculosis for novel drug discovery
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Characterizing septum inhibition in Mycobacterium tuberculosis for novel drug discovery
چکیده انگلیسی

SummaryA temperature sensitive mutation in the cell division protein FtsZ was used in combination with transcriptional analysis to identify biomarkers for inhibition of septum formation. Crystallography and modeling revealed that the glycine for aspartate substitution at amino acid 210 was located in helix 8 of the protein, adjacent to the T7 synergy loop. To verify the molecular behavior of FtsZD210G, the in vitro activity and structural stability were evaluated as a function of temperature. These analyses confirmed that the FtsZD210G mutant had reduced GTPase and polymerization activity compared to wild-type FtsZ, and CD spectroscopy demonstrated that both FtsZD210G and wild-type FtsZ had similar structure and stability. Significantly, the FtsZD210G merodiploid strain of M. tuberculosis had compromised growth at 37 °C, substantiating the suitability of FtsZD210G as a molecular tool for global analysis in response to improper FtsZ polymerization and septum inhibition. Advanced model-based bioinformatics and transcriptional mapping were used to identify high-content multiple features that provide biomarkers for the development of a rational drug screening platform for discovering novel chemotherapeutics that target cell division.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tuberculosis - Volume 88, Issue 5, September 2008, Pages 420–429
نویسندگان
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