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The respiratory chain of M. tuberculosis
Author(s) -
Rubin Harvey
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a207-b
Subject(s) - respiratory chain , mycobacterium tuberculosis , context (archaeology) , oxidoreductase , enzyme , biology , microbiology and biotechnology , gene , bacteria , tuberculosis , biochemistry , genetics , medicine , paleontology , pathology
Type II NADH oxidoreductase (NDH‐2), the initial step in the electron transport respiratory chain, is a critical enzyme in the life cycle of Mycobacterium tuberculosis (Mtb), the bacterium that kills more people world‐wide than any other bacterial organism. The central role of NDH‐2 in Mtb is supported by extensive evidence from biochemical and transcriptional studies, gene network analysis, gene deletion analysis, investigation of bacterial growth in various media and under various culture conditions, and animal experiment. Not only is NDH‐2 an important enzyme in its biomedical context, it is has certain unique biochemical and structural properties compared to other bacterial type II NADH oxidoreductases. We will discuss the ping pong tetra‐uni mechanism of wild‐type NDH‐2. Given the emergence of extremely resistant strains of M. tuberculosis, new therapeutic agents need to be identified and developed. We will present data on phenothiazines which are non‐competitive inhibitors of wild‐type Mtb NDH‐2 with respect to NADH whereas the inhibition is uncompetitive with respect to Q2.