Structure-Guided Optimization of Inhibitors of Acetyltransferase Eis from Mycobacterium tuberculosis
Explore the source record for details and available documents.
Punetha, Ankita↗
Engineering topics
Ngo, Huy X.
Publications and source records attributed to Ngo, Huy X..
Potent 1,2,4-Triazino[5,6 b ]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis
A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase that multiacetylates KAN and other aminoglycosides, rendering them unable to bind the bacterial ribosome. By high-throughput screening, a series of substituted 1,2,4-triazino[5,6 b ]indole-3-thioether molecules were identified as effective Eis inhibitors. In this work, we purchased 17 and synthesized 22 new compounds, evaluated their potency, and characterized their steady-state kinetics. Four inhibitors were found not only to inhibit Eis in vitro , but also to act as adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal structure of Eis in complex with a potent inhibitor and CoA shows that the inhibitors bind in the aminoglycoside binding site snugly inserted into a hydrophobic cavity. These inhibitors will undergo preclinical development as novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.
60 APPLIED LIFE SCIENCES↗
Instrumentation and robotic image processing using top-down model control
A top-down image processing scheme is described. A three-dimensional model of a robotic working environment, with robot manipulators, workpieces, cameras, and on-the-scene visual enhancements is employed to control and direct the image processing, so that rapid, robust algorithms act in an efficient manner to continually update the model. Only the model parameters are communicated, so that savings in bandwidth are achieved. This image compression by modeling is especially important for control of space telerobotics. The background for this scheme lies in an hypothesis of human vision put forward by the senior author and colleagues almost 20 years ago - the Scanpath Theory. Evidence was obtained that repetitive sequences of saccadic eye movements, the scanpath, acted as the checking phase of visual pattern recognition. Further evidence was obtained that the scanpaths were apparently generated by a cognitive model and not directly by the visual image. This top-down theory of human vision was generalized in some sense to the frame in artificial intelligence. Another source of the concept arose from bioengineering instrumentation for measuring the pupil and eye movements with infrared video cameras and special-purpose hardware.
Stark, Lawrence↗