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Received August 18, 2010; Revision received October 13, 2010
Most mycobacteria appear to be naturally resistant to β-lactam antibiotics such as penicillin. However, very few β-lactamases and their regulation have been clearly characterized in Mycobacterium tuberculosis H37Rv. In this study, a unique bifunctional protein, Rv2752c, from M. tuberculosis showed both β-lactamase and RNase activities. Two residues, D184 and H397, appear to be involved in Zn2+-binding and are essential for the dual functions. Both activities are lost upon deletion of the C-terminal 100 a.a. long Rv2752c tail, which contains an additional loop when compared with the RNase J of Bacillus subtilis. A chaperone-like protein, Rv2373c, physically interacted with Rv2752c and inhibited both activities. This is the first report of characterization of a bifunctional β-lactamase and its regulation in mycobacteria. These data offered important clues for further investigation of the structure and function of microbial β-lactamases. Increased understanding of this protein will provide further insights into the mechanism of microbial drug resistance.
KEY WORDS: Mycobacterium tuberculosis, metallo-β-lactamase, ribonuclease