Exploring the interaction between monochloroacetic acid and transglutaminase: Spectroscopic analysis, computational...

Area of Science:

• Biochemistry
• Toxicology
• Spectroscopy

Background:

• Environmental exposure to monochloroacetic acid (MCA), a disinfection byproduct, presents a public health concern.
• MCA interacts with skin barrier proteins, potentially compromising epidermal integrity.

Purpose of the Study:

• To investigate the interaction between MCA and transglutaminase (TGase), an enzyme crucial for skin barrier function.
• To elucidate the molecular mechanisms underlying MCA's dermal toxicity.

Main Methods:

• Utilized a spectroscopy-based integrative strategy, including UV-vis absorption and various fluorescence spectroscopy techniques.
• Employed molecular docking and molecular dynamics simulations to analyze MCA-TGase interactions.
• Conducted in vitro assays to assess TGase activity and epidermal barrier function.

Main Results:

• MCA binds to TGase via hydrogen bonding and van der Waals forces, inducing conformational changes and altering the enzyme's microenvironment.
• The binding process is spontaneous, with MCA interacting with catalytic residues Asp255 and His274.
• MCA binding enhances TGase flexibility, leading to altered activity and impaired epidermal barrier function.

Conclusions:

• Elucidates the structure-function relationship of the MCA-TGase interaction.
• Provides molecular-level insights into the dermal toxicity of MCA.
• Highlights the potential health risks associated with MCA exposure through skin contact.