Structural highlights
Function
[EIS_MYCTU] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.[1]
Publication Abstract from PubMed
The emergence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (TB) is a serious global threat. Aminoglycoside antibiotics are used as a last resort to treat XDR-TB. Resistance to the aminoglycoside kanamycin is a hallmark of XDR-TB. Here, we reveal the function and structure of the mycobacterial protein Eis responsible for resistance to kanamycin in a significant fraction of kanamycin-resistant Mycobacterium tuberculosis clinical isolates. We demonstrate that Eis has an unprecedented ability to acetylate multiple amines of many aminoglycosides. Structural and mutagenesis studies of Eis indicate that its acetylation mechanism is enabled by a complex tripartite fold that includes two general control non-derepressible 5 (GCN5)-related N-acetyltransferase regions. An intricate negatively charged substrate-binding pocket of Eis is a potential target of new antitubercular drugs expected to overcome aminoglycoside resistance.
Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB.,Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-Tsodikova S Proc Natl Acad Sci U S A. 2011 May 31. PMID:21628583[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wei J, Dahl JL, Moulder JW, Roberts EA, O'Gaora P, Young DB, Friedman RL. Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J Bacteriol. 2000 Jan;182(2):377-84. PMID:10629183
- ↑ Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-Tsodikova S. Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB. Proc Natl Acad Sci U S A. 2011 May 31. PMID:21628583 doi:10.1073/pnas.1105379108
