Hydrogen-bonding classes in proteins and their contribution to the unfolding reaction.
This paper proposes to assess hydrogen-bonding contributions to the protein stability, using a set of model proteins for which both X-ray structures and calorimetric unfolding data are known. Pertinent thermodynamic quantities are first estimated according to a recent model of protein energetics based on the dissolution of alkyl amides. Then it is shown that the overall free energy of hydrogen-bond formation accounts for a hydrogen-bonding propensity close to helix-forming tendencies previously found for individual amino acids. This allows us to simulate the melting curve of an alanine-rich helical 50-mer with good precision. Thereafter, hydrogen-bonding enthalpies and entropies are expressed as linear combinations of backbone-backbone, backbone-side-chain, side-chain-backbone, and side-chain-side-chain donor-acceptor contributions. On this basis, each of the four components shows a different free energy versus temperature trend. It appears that structural preference for side-chain-side-chain hydrogen bonding plays a major role in stabilizing proteins at elevated temperatures.
Ragone
R
R
Dipartimento di Biochimica e Biofisica and CRISCEB, Seconda Università di Napoli, Naples, Italy. ragone@unina2.it
D006801:Humans; D006860:Hydrogen Bonding; D009113:Muramidase / Q000737:chemistry; D009211:Myoglobin / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry*; D011489:Protein Denaturation; D017510:Protein Folding; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry*; D014361:Trypsin Inhibitors; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D009211:Myoglobin; D010940:Plant Proteins; D014361:Trypsin Inhibitors; D000516:alpha-Amylases; D009113:Muramidase; D014357:Trypsin