Solving the catalytic pathway of antibiotic resistance

June 25, 2013

First identified in the bacteria Klebsiella pneumonia, a novel enzyme NDM-1 hydrolyzes and inactivates nearly all antibiotics with startling efficiency.

In a combined structural, biochemical and theoretical study by Argonne researchers, the catalytic pathway of inactivation was elucidated using X-ray crystallography, biochemical assays and numerical simulation.

The NDM-1 enzyme was found to interact with antibiotics solely through zinc ions, or other metals bound in the active site. The zinc ions also were found to activate hydrolysis of the antibiotic. Understanding how NDM-1works is the first step in creating new antibiotics that can remain active in its presence.

To learn more, read the entire paper titled NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism.

Kim Y, Cunningham MA, Mire J, Tesar C, Sacchettini J, Joachimiak A. NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism. FASEB J. 2013 May;27(5):1917-27.