title: Characterization of a bifunctional β-lactamase/ribonuclease and its interaction with a chaperone-like protein in the pathogen Mycobacterium tuberculosis H37Rv.
abstract: 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 Zn(2+)-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.
authors.affiliation: National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Zheng-Guo
authors.initials: ZG
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism*; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; D012260:Ribonucleases; D001618:beta-Lactamases