AI Article Synopsis
- The study focuses on the enzyme transglutaminase from Streptomyces mobaraensis (MTG), which is commonly used to alter therapeutic proteins.
- Researchers crystallized MTG with an inhibitory peptide (DIPIGSKMTG) to understand how it binds to glutamine donor substrates, leading to a detailed structure that was only provided by this specific peptide.
- The findings indicate that the peptide binds in a specific way within MTG's cleft, suggesting a "zipper-like" mechanism for how substrate proteins are cross-linked by the enzyme.
Article Abstract
The protein cross-linking enzyme transglutaminase from Streptomyces mobaraensis (MTG) is frequently used to modify therapeutic proteins. In order to reveal the binding mode of glutamine donor substrates, we have now crystallized MTG covalently linked to large inhibitory peptides. A series of peptide structures were examined but DIPIGSKMTG, which was chloroacetylated at serine, was the only inhibitory molecule that resulted in an interpretable density map. We found that, besides the warhead (modified Ser6), Ile4 and Gly5 of the inhibitory peptide occupy the tight but extended hydrophobic bottom of the MTG-binding cleft. Both termini of the peptide protrude along the cleft walls almost perpendicular to the bottom of the extended cleft. This peptide model suggests a zipper-like cross-linking mechanism of self-assembled substrate proteins by MTG.
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| http://dx.doi.org/10.1111/febs.14678 | DOI Listing |
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