Hosted by Dr. Oliver Medvedik, the May edition of Journal Club will focus on the recent publication by the Spiegel Lab at Yale University where two forms of advanced glycation end products were successfully cleaved. We already discussed this important breakthrough in our article – Reversal of Two Advanced Glycation End Products Achieved. Now we will be taking a deeper look at the data during the journal club.
This live show will be streamed to our Facebook page at 13:00 EDT on the 28th of May and is supported thanks to our monthly patrons – The Lifespan Heroes.
Abstract
Advanced glycation end products (AGEs) are a heterogeneous group of molecules that emerge from the condensation of sugars and proteins via the Maillard reaction. Despite a significant number of studies showing strong associations between AGEs and the pathologies of agingβrelated illnesses, it has been a challenge to establish AGEs as causal agents primarily due to the lack of tools in reversing AGE modifications at the molecular level. Here, we show that MnmC, an enzyme involved in a bacterial tRNAβmodification pathway, is capable of reversing the AGEs carboxyethylβlysine (CEL) and carboxymethylβlysine (CML) back to their native lysine structure. Combining structural homology analysis, siteβdirected mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in free amino acid form. We show that this enzyme variant is also active on a CELβmodified peptidomimetic and an AGEβcontaining peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE). Our data demonstrate that MnmC variants are promising lead catalysts toward the development of AGEβreversal tools and a better understanding of AGE biology.
Reference
Kim, N. Y., Goddard, T. N., Sohn, S., Spiegel, D. A., & Crawford, J. (2019). Biocatalytic Reversal of Advanced Glycation End Product Modification.Β ChemBioChem.
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