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Importance in Health

Lead is an extremely toxic agent and is a commonly used heavy metal. In humans, over exposure to lead raises the levels of lead in the biological system and has been linked to numerous health disorders ^[1] . The effects of lead exposure can affect reproductive systems, nervous system, and carcinogenicity ^[2] . However, the pathway in which lead affects the body in each case is not known. Therefore, the discovery of leadzyme allows the lead-induced disorders to be further understood.

History

Leadzyme was discovered by Uhlenbeck and co-worked in 1992, while they were searching for RNAs that cleaved in the presence of lead ^[3] . The discovery was by in vitro selection, which allows for an isolation and amplification of selected functional molecules. This method has been key in the discovery of numerous RNA and DNA catalysis. Leadzyme, or lead-dependent ribozyme, is among the smallest known catalytic RNAs ^[3] .

Function

Leadzyme is a relatively small catalytic RNA that uses a unique two-step reaction to cleave within the active site ^[4] . In the presence of Pb^2+, it catalyzes the cleavage of the C6-C7 phosphodiester bond ^[3] . This is accomplished via nucleophilic attack ^[3] . The resulting in a 2', 3'-cyclic phosphate and a 5'-hydroxyl terminus ^[3] . The nuclear magnetic resonance spectrospcopy (NMR) and crystal structure of leadzyme has been used to try to better understand the cleavage reaction process ^[3] . However, neither data sets revealed the proposed in-line alignment for attack by the 2'-OH nucleophilic group as described experimentally ^[4]