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Ionic liquids (ILs) are known to provide stability to biomolecules. ILs are also widely used in the fields of chemical engineering, biological engineering, chemistry, and biochemistry because they facilitate enzyme catalyzed reactions and enhance their conversion rate. In this work, we have evaluated the influence of alkyl chain substitution of ammonium ILs such as diethylammonium dihydrogen phosphate (DEAP) and triethylammonium hydrogen phosphate (TEAP) for the stability and activity of the tobacco etch virus (TEV) protease. Further, we performed molecular dynamics (MD) simulations to calculate the RMSD (root mean square deviation) for TEV and TEV + ILs. Experimental and simulations results show that TEV is more stable in the presence of TEAP than DEAP. Whereas, TEV protease activity for the cleavage of fusion proteins is preserved in the presence of DEAP while lost in the presence of TEAP. Hence, DEAP IL can serve as alternative solvents for the stability of the TEV protease with preserved activity. To the best of our knowledge, this is first study to show that ILs can stabilize and maintain the TEV protease cleavage activity.

Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development. Here, we determined the first crystal structure of the Dvl-1 PDZ domain at a resolution of 1.76 Å, and compared it with its previously reported solution structure. The Dvl1 PDZ domain crystal belonged to the space group H32 with unit-cell parameters a = b = 72.837, c = 120.616, α = β = 90.00, γ = 120.00. The crystal structure of Dvl1 PDZ shared its topology with the previously reported structure determined by nuclear magnetic resonance (NMR); however, the crystal structure was quite different from the solution structure in both the secondary structural region and the ligand-binding pocket. Molecular modeling based on NMR and X-ray crystallographic data yielded detailed information about the Dvl1/CXXC5 interaction, which will be useful for designing inhibitors.

Surgical exposure for massive tumor of the anterior skull base can be difficult. We have combined two surgical approaches, the subfrontal/subcranial approach and the Le Fort I osteotomy approach, to provide panoramic accesses to the anterior skull base. Via this combination of exposures, we have easily accessed and resected tumors extending from the cribiform plate all the way down to the level of the upper cervical spine. Additionally, we have used the nasal endoscope and microscope to assist in our resection. This approach has several advantages, which include ease of post-resection skull base reconstruction and excellent cosmetic results by avoiding anterior facial incisions. We believe this approach should be in the armamentarium of any surgeon resecting massive anterior skull base tumor.