[Proteolytic degradation of native hemoglobin and its constituent parts--isolated subunits and globin. II. Correlation with the hydrogen exchange data and the mechanism of the burst-like proteolytic breakdown of native proteins].
Basing on comparison of the data on the rate of proteolytic breakdown and hydrogen exchange for hemoglobin and its constituent parts, we discuss the problem of the mechanism of the burst-like ("one-by-one") proteolytic breakdown of native proteins in conditions which are not close to extreme denaturational. The rate of proteolytic breakdown by different proteases decreases in the same order as the local conformational mobility according to the hydrogen exchange data: globin greater than oxy-alpha-chain greater than metHb much greater than oxy-beta-chain greater than HbO2 congruent to CNmetHb. For native globin and and metHb, the rates of hydrogen exchange and proteolytic breakdown depend weakly on the temperature in the range of 5-25 degrees, not much stronger than for flexible "unstructured" peptides and proteins. These correlations as well as other data allow a conclusion to be made that the process of the proteolytic breakdown of native proteins study is governed by spontaneous local conformational transitions of the same type as for the hydrogen exchange processes. A similar correlation between the changes in the rates of hydrogen exchange and proteolytic thought that the discussed mechanism of the burst-like proteolytic breakdown has a common character. Alongside with similarities, we consider distinctions between the role of the dynamical structure of the proteins in the realization of reactions of proteolytic degradation and the hydrogen exchange. Upon proteolytic degradation of stable native proteins, the significance of conformational rearrangement of the protein substrate induced by proteases and also that of distortions in the spatial structure of proteases under the action of the protein substrate increase. It is pointed that the actual concentration of the dynamic conformers of native proteins which serve as substrate for proteases can be much lower than the nominal concentration of the protein substrate. The mechanisms of the influence of the cofactor splitting and the dissociation of the oligomeric structure on the rate of proteolytic degradation are discussed.
D004355:Drug Stability; D005914:Globins; D006454:Hemoglobins; D006801:Humans; D007700:Kinetics; D010447:Peptide Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013696:Temperature
D006454:Hemoglobins; D005914:Globins; D010447:Peptide Hydrolases
Proteoliticheskaia degradatsiia nativnogo gemoglobina i ego sostavnykh chasteĭ--izolirovannykh sub"edinits i globina. II. Korreliatsiia s dannymi vodorodnogo obmena i mekhanizm vzryvoobraznogo proteoliticheskogo rasshchepleniia nativnykh belkov.