Ser-Glu

Serine proteases comprise nearly one-third of all known proteases identified to date and play crucial roles in a wide variety of cellular as well as extracellular functions, including the process of blood clotting, protein digestion, cell signaling, inflammation, and protein processing. Their hallmark is that they contain the so-called "classical" catalytic Ser/His/Asp triad. Although the classical serine proteases are the most widespread in nature, there exist a variety of "nonclassical" serine proteases where variations to the catalytic triad are observed. Such variations include the triads Ser/His/Glu, Ser/His/His, and Ser/Glu/Asp, and include the dyads Ser/Lys and Ser/His. Other variations are seen with certain serine and threonine peptidases of the Ntn hydrolase superfamily that carry out catalysis with a single active site residue. This work discusses the structure and function of these novel serine proteases and threonine proteases and how their catalytic machinery differs from the prototypic serine protease class.

Scope: Val-Ser-Glu-Glu (VSEE), identified from duck egg white peptides, has been proven to facilitate calcium absorption in a previous study. Since prevention of osteoporosis is important, it might act as a potential cofactor in osteoporosis prevention. Therefore, the aim of this study is to investigate the regulation of VSEE on osteoporosis and abnormal lipid metabolisms. Methods and results: MC3T3-E1 cell and ovariectomized (OVX) rat model are used to evaluate VSEE on regulation of bone and lipid metabolisms. Differentiation and matrix mineralization of preosteoblast are significantly increased by VSEE (p <0.05), which attributed to stimulating calcium influx, then to activating Wnt/β-catenin signaling pathway and regulating runt-related transcription factor 2 and osteoprotegerin. VSEE can cross Caco-2/HT-29 co-cultured monolayer via paracellular pathway and peptide transporter 1 (PepT1), and can be detected in blood and maximum concentration is 122.84 ± 3.68 mg L-1 at 60 min. Additionally, VSEE reverses bone loss and regulate dyslipidemia through Wnt/β-catenin signaling pathway in OVX rats. Firmicutes phylum, Veillonellaceae, Prevotellaceae and six genera in VSEE group are significantly different compared with the Model group (p < 0.05). Conclusion: VSEE promotes bone growth and inhibit abnormal lipid metabolism in an OVX model through the regulation of intestinal microbiota compositions and Wnt/β-catenin signal pathway.

Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser-Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser-Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser-Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications.