Enzymatic Analysis of New In Silico Derived Allosteric Inhibitors of Bacterial MTN

Document Type

Student Presentation

Presentation Date

April 2017

Faculty Sponsor

Ken Cornell


The emergence of drug resistance requires the development of new antibiotics with novel mechanisms of action. One potential drug target is the unique bacterial enzyme 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTN), which is required to salvage adenine and methionine used in S-adenosylmethionine (SAM) dependent reactions, and plays an important role in bacterial virulence. In this study, we examined the effects of proposed inhibitors that bind a potential allosteric or alternate binding site on MTN activity. These inhibitors were selected using in silico screening of the Zinc-in-Man compound database, which includes FDA-approved drugs. Of the thirty-six compounds identified as potential inhibitors, ten were found to affect MTN activity using a spectrophotometric assay. Of these compounds four were found to be mixed inhibitors of MTN with low micromolar inhibition constants. Results of our investigation are being used to establish a structure-activity relationship that will be useful in the design of novel antibiotics to treat bacterial infections.

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