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Contents |
Leadzyme
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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
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] Therefore: it is hypothesized that the structures represent ground states of leadzyme and are not catalytically active. [4]
Structural Highlights
Leadzyme, unlike other catalyic RNAs, can differ in sequences that are compatible with catalysis [3]. This is due to only three bases being required for catalysis to occur: . [3] Another important structural difference between leadzyme and other catalytic RNAs is a at the cleavage site. This pucker increases the catalytic rate of leadzyme.
References
- ↑ Barciszewska MZ, Szymanski M, Wyszko E, Pas J, Rychlewski L, Barciszewski J. Lead toxicity through the leadzyme. Mutat Res. 2005 Mar;589(2):103-10. doi: 10.1016/j.mrrev.2004.11.002. Epub 2004, Dec 23. PMID:15795164 doi:http://dx.doi.org/10.1016/j.mrrev.2004.11.002
- ↑ Klotz K, Goen T. Human Biomonitoring of Lead Exposure. Met Ions Life Sci. 2017 Apr 10;17. pii:, /books/9783110434330/9783110434330-006/9783110434330-006.xml. doi:, 10.1515/9783110434330-006. PMID:28731299 doi:http://dx.doi.org/10.1515/9783110434330-006
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Hoogstraten CG, Legault P, Pardi A. NMR solution structure of the lead-dependent ribozyme: evidence for dynamics in RNA catalysis. J Mol Biol. 1998 Nov 27;284(2):337-50. PMID:9813122 doi:S0022-2836(98)92182-9
- ↑ 4.0 4.1 4.2 Qi X, Xia T. Structure, dynamics, and mechanism of the lead-dependent ribozyme. Biomol Concepts. 2011 Aug 1;2(4):305-14. doi: 10.1515/bmc.2011.029. PMID:25962038 doi:http://dx.doi.org/10.1515/bmc.2011.029
