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Updated: Sep 28, 2025

Structural Biology and Analytical Chemistry Approaches for Characterizing C-Glycoside Metabolic Enzymes in Human Gut Microbiota
Published on: May 23, 2025
Crystal structures of human glyoxalase I and its complex with TLSC702 reveal inhibitor binding mode and substrate
Midori Usami1, Koki Ando1, Asuka Shibuya1
1Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Abstract:
Human glyoxalase I (hGLO I) is an enzyme for detoxification of methylglyoxal (MG) and has been considered an attractive target for the development of new anticancer drugs. In our previous report, the GLO I inhibitor TLSC702 induced apoptosis in tumor cells. Here, we determined the crystal structures of hGLO I and its complex with TLSC702. In the complex, the carboxyl O atom of TLSC702 is coordinated to Zn2+ , and TLSC702 mainly shows van der Waals interaction with hydrophobic residues. In the inhibitor-unbound structure, glycerol, which has similar functional groups to MG, was bound to Zn2+ , indicating that GLO I can easily bind to MG. This study provides a structural basis to develop better anticancer drugs.
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