Disulfide-Centered Hydrogen Bonding: Insights from Protein Structure Analysis and IR-UV Double Resonance Spectroscopy

Area of Science:

• Biochemistry
• Structural Biology
• Chemical Physics

Background:

• Disulfide bonds are crucial in protein structure, but noncovalent interactions involving their sulfur atoms, especially sulfur-centered hydrogen bonds (H-bonds), are not well understood.
• Experimental characterization of these sulfur-centered H-bonds is limited, hindering a complete understanding of their role in biological systems.

Purpose of the Study:

• To experimentally investigate and characterize sulfur-centered hydrogen bonds involving disulfide bonds in proteins.
• To provide benchmark data for refining computational models of protein interactions.

Main Methods:

• Analysis of Protein Data Bank (PDB) structures to identify potential sulfur-centered H-bonds.
• Quantum chemical calculations on model systems.
• Gas-phase vibrational spectroscopy (mass-selective electronic and IR spectroscopy) of a model complex (p-cresol-dimethyl disulfide).

Main Results:

• Approximately 20% of protein structures contain disulfide bonds, with numerous potential O-H···S and N-H···S H-bonds identified.
• O-H···S H-bonds were found to be shorter and more directional than N-H···S H-bonds.
• Experimental spectroscopy confirmed disulfide-centered H-bonds and provided quantitative data on their strength, comparable to other H-bond acceptors.

Conclusions:

• Sulfur-centered hydrogen bonds involving disulfide bonds are experimentally validated and quantifiable.
• The findings provide crucial data for computational chemistry and enhance the understanding of disulfide bond roles in protein structure and function.