Nanjing Normal University School of Chemistry and Material Science Professor Zhiyuan Gu’s team (http://www.zygulab.com/) and Professor Hongcai Zhou from Texas A&M University had new findings on the two-dimensional metal-organic framework (2-D MOF) nanosheets as an enzyme inhibitor.
MOFs with high specific surface areas, tunable pores, and diverse functionalities have been explored extensively for gas adsorption and separation, energy storage, catalyst, and carbon dioxide capture. Recently, MOFs were utilized in the stabilization of enzymes for catalysis in extreme conditions as well as in biomedical applications, such as drug delivery, bioimaging, and photodynamic therapy. Although the applications are in diverse fields, understanding the fundamentals of MOF–protein interactions will be the key of developing these technologies.
Professor Gu’s team, together with Professor Zhou focused on the modulation of enzyme activity within the MOF–bio interface. Considering that bulk crystals of MOFs give inhomogeneous dispersion in water while nanoscale MOFs easily form aggregates in solution, which hinders the analysis, research team employed 2-D MOF nanosheets to form a MOF–bio interface for they have good dispersibility and large surface areas for adequate protein binding. α-Chymotrypsin (ChT, EC 18.104.22.168) was selected as model enzyme because it is an important serine protease in the alimentary canal and its structure has been well characterized. Two MOF nanosheets with different metals were synthesized for research.One is 2-D Zn2 (bim)4 (bim = benzimidazole) nanosheets, while the other is Cu-based 2-D MOF nanosheets (Figure 1a,b), namely, Cu (bpy)2 (OTf) 2 (Cu-MOF, bpy = 4,4-bipyridine, OTf = trifluoromethanesulfonate).By changing buffer and ionic strength, calculating Km and investigating Ch Tsecondary structure, they finally found that the activity of ChT can be effectively inhibited by 2-D Cu (bpy) 2 (OTf)2 nanosheets.
Research showed that the activity of ChT can be effectively inhibited with 96.9% inhibition by 2-D Cu (bpy) 2 (OTf)2 nanosheets, while Zn2 (bim)4 nanosheets show no significant inhibition effect toward ChT. Kinetic studies revealed that the material acts as a competitive inhibitor toward ChT. Furthermore, fluorescence and circular dichroism spectroscopy reveal that the 2-D MOF nanosheets do not change the secondary structure of the enzyme. The Cu(II) center of the 2-D nanosheets binds the4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) molecules in the buffer, leading to an electrostatic interaction between the nanosheets and the enzyme. In addition, the irreversible coordination interactions between Cu (II) center and His-57 played an important role during the inhibition process, as supported by ionic strength experiments and UV absorbance changes of Cu(II) d–d transitions. As a result, the substrate is prevented from reaching the active sites of the enzyme causing enzyme inhibition.
The related research results are published on Journal of the American Chemical Society (JACS, 139 (24), 8312–8319) entitled “Two-Dimensional Metal-Organic Framework Nanosheets as an Enzyme Inhibitor: Modulation of the α-Chymotrypsin Activity”.
Professor Zhiyuan Gu focuses on the MOFs research, including MOFs as catalyst, Nanosized MOFs, MOF membranes. He has published many research articles on international chemistry journals such as Sci. Rep., Angew. Chem. Int. Ed. and J. Am. Chem. Soc. He was named the ‘Jiangsu Distinguished Professor’ and the ‘Young Elite Scientist CAST’.
Ming Xu, the first author of this paper, is a first year graduate student at the School of Chemistry and Material Science and the co-first author is a Ph. D student named Shuai Yuan from Texas A&M University. During her undergraduate studies, Ming Xu has won the grand prize of “Dow Chemical Cup Experiment Contest for College Students in East China Chemistry and Chemical Engineering League”, first prize of the forth Chemistry Experiment Invitational for College Students in Normal Universities in China and ‘Excellent Graduate Thesis Award in NNU. During her postgraduate period, she won Excellent Posters Award’ twice in both domestic and international academic conferences.