Fig. 23 | The Journal of Antibiotics

Fig. 23

From: Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors

Fig. 23

Inhibition of bacterial salicylate adenylation enzymes. a Salicylate adenylation enzymes, such as MbtA, catalyze adenylation of salicylate (23.1) to form a salicyl-AMP intermediate (23.2), which reacts with a phosphopantetheine thiol nucleophile on an ArCP domain, such as that in MbtB, to form a salicyl-PCP thioester product (23.3), en route to aryl-capped siderophores, such as M. tuberculosis mycobactin T (23.4). b A salicyl-AMS inhibitor (23.5) mimics the salicyl-AMP intermediate (23.2) and exhibits in vivo efficacy in a mouse model of tuberculosis. A constrained cinnolinone analogue (23.6) has improved pharmacological properties

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