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protein inhibition
2) A large class of antibiotics, like penicillin, for example, contain a B- ...
protein inhibition
2) A large class of antibiotics, like penicillin, for example, contain a B-lactam ring. penicillin These antibiotics inhibit bacterial growth by interfering with cell wall synthesis. A common resistance mechanism that bacteria have evolved in recent years is the detoxification of antibiotics by a series of enzymes called ?-lactamases, which specifically cleave the ? lactam ring. Some ?-lactamases act by nucleophilic attack of an activated serine on the carbonyl group of the B-lactam ring, forming a covalent enzyme intermediate that is subsequently hydrolyzed for recycling of the enzyme (see figure below). To counteract this resistance mechanism, suicide substrates like Tazobactam stay covalently attached to enzymes. Metallo-B-lactamases are another class of B-lactamases that contain one or two Zn2+ ions in their active sites (see figure to the right) and are prevalent in drug-resistant bacteria. A. What is the role of the Zn2+ ion in the catalytic mechanism of the metalle- 3 -lactamases? What is the role of the water molecule? Please describe in a couple of sentences the catalytic cycle of such enzymes. B. Will Tazobactam be an effective inhibitor of this metalle-B-lactamase? Why or why not? C. Considering the design of putative next-generation inhibitors of metalle- B-lactamases. what will you want such inhibitors to be able to do to become effective against metalleB-lactamases?