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Journal Club May 2019 – AGE Breakers

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For the May Journal Club, Dr. Medvedik and guests took a look at the recent publication by the Spiegel Lab at Yale University where two forms of advanced glycation end products (AGEs) were successfully cleaved.

We also covered this important breakthrough in our article – Reversal of Two Advanced Glycation End Products Achieved.

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 aging‐related 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 tRNA‐modification pathway, is capable of reversing the AGEs carboxyethyl‐lysine (CEL) and carboxymethyl‐lysine (CML) back to their native lysine structure. Combining structural homology analysis, site‐directed 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 CEL‐modified peptidomimetic and an AGE‐containing 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 AGE‐reversal 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. ChemBioChem.

CategoryJournal club
About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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