3R1K

Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis H37Rv in complex with CoA and an acetamide moiety

Summary for 3R1K

• Entry DOI: 10.2210/pdb3r1k/pdb
• Descriptor: Enhanced intracellular survival protein, COENZYME A, ACETAMIDE, ... (4 entities in total)
• Functional Keywords: gnat, acetyltransferase, transferase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 47519.50

Authors

Biswas, T.,Chen, W.,Garneau-Tsodikova, S.,Tsodikov, O.V. (deposition date: 2011-03-10, release date: 2011-06-01, Last modification date: 2024-02-21)

Primary citation

Chen, W.,Biswas, T.,Porter, V.R.,Tsodikov, O.V.,Garneau-Tsodikova, S.
Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB.
Proc.Natl.Acad.Sci.USA, 108:9804-9808, 2011

PubMed Abstract: 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.

PubMed: 21628583
DOI: 10.1073/pnas.1105379108

Experimental method

X-RAY DIFFRACTION (1.95 Å)