Figure 1: NDM-1 in complex with hydrolyzed ampicillin. Stereoview of the active site, with carbon atoms in the protein shown in cyan; those in the substrate are pink. Nitrogen atoms are blue, oxygen atoms are red, sulfur atoms are yellow, and zinc ions are magenta. An oriented water molecule (W) is gray. The Fo-Fc electron density around the substrate is contoured at 3σ. Dashed lines indicate key interactions between the protein and zinc ions.
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.