Crystal structures of human glyoxalase I and its complex with TLSC702 reveal inhibitor binding mode and substrate preference.
FEBS Lett
; 596(11): 1458-1467, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35363883
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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Base de dados:
MEDLINE
Assunto principal:
Lactoilglutationa Liase
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article