Charge redistribution in proteins via linear hydrogen-bond chains.

Area of Science:

• Biochemistry
• Structural Biology
• Chemical Biology

Background:

• Proteins play crucial roles in biological processes.
• Understanding protein-substrate interactions is key to deciphering enzyme mechanisms.

Purpose of the Study:

• To propose and validate a mechanism for protein-mediated substrate activation.
• To investigate the role of hydrogen-bond chains in facilitating proton dynamics and charge separation.

Main Methods:

• Survey of published X-ray diffraction structures.
• Identification of hydrogen-bond chains linked to substrates, co-factors, or metal ions.
• Analysis of proposed proton dynamics within protein mechanisms.

Main Results:

• Validated the existence of structural arrangements involving hydrogen-bond chains emanating from bound molecules.
• Identified specific examples in proteins like carboxypeptidase A and carbonic anhydrase.
• Demonstrated how concerted proton shifts lead to charge separation and atom activation.

Conclusions:

• Hydrogen-bond chains are critical for protein-mediated substrate activation.
• Proton tautomeric shifts within these chains generate nucleophilic or electrophilic centers.
• This mechanism provides insight into the catalytic power of various enzymes.