5ec4 | pdb_00005ec4

Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis in complex with inhibitor 13g and CoA

spinqualitylabelsall models 5ec4, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ec4 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.21Å Ligands: 5LQ, COA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EIS_MYCTU May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection. Publication Abstract from PubMed A major cause of tuberculosis (TB) resistance to the aminoglycoside kanamycin (KAN) is the Mycobacterium tuberculosis (Mtb) acetyltransferase Eis. Upregulation of this enzyme is responsible for inactivation of KAN through acetylation of its amino groups. A 123000-compound high-throughput screen (HTS) yielded several small-molecule Eis inhibitors that share an isothiazole S,S-dioxide heterocyclic core. These were investigated for their structure-activity relationships. Crystal structures of Eis in complex with two potent inhibitors show that these molecules are bound in the conformationally adaptable aminoglycoside binding site of the enzyme, thereby obstructing binding of KAN for acetylation. Importantly, we demonstrate that several Eis inhibitors, when used in combination with KAN against resistant Mtb, efficiently overcome KAN resistance. This approach paves the way toward development of novel combination therapies against aminoglycoside-resistant TB. Potent Inhibitors of Acetyltransferase Eis Overcome Kanamycin Resistance in Mycobacterium tuberculosis.,Willby MJ, Green KD, Gajadeera CS, Hou C, Tsodikov OV, Posey JE, Garneau-Tsodikova S ACS Chem Biol. 2016 Apr 7. PMID:27010218 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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