The protein backbones are shown in a ribbon style, with coordinating residues shown as sticks and colored by element carbons in gray. Botulinum neurotoxin BoNTthe source of Botulism disease, is secreted by the Gram-positive Clostridium botulinum bacteria, and is the deadliest substance known to humankind, with a single gram of the toxin being able to kill over 1 million people. Further work derivatizing celecoxib-like inhibitor cores with MBPs resulted in compounds such as 5-LOi-5, licofelone, and Tepoxalin. Despite these limitations, MetLigDB is a useful resource for its ability to organize search results according to MBP and metal ion, which lends itself to assisting in the development of new metalloenzyme inhibitors as the creators intended. The development of 4-methylpyrazole itself is an example of even a simple MBP serving as a therapeutic, identified from imidazole, then utilizing small substituents to modulate and improve affinity, and finally simple derivatization to obtain the needed efficacy and low toxicity. Rpn11 is a metalloprotease in the greater deubiquitinating enzyme DUB family.
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