Proteolysis studies

With the support of quantum mechanics this proteolysis study has readily shown that fluorinated amino acid side chains are able to direct enzyme substrate interactions, which can have an influence on proteolytic stability. Depending on the absolute stereochemistry and on the position within the sequence, aTfm amino acids can considerably stabilize peptides against proteolysis. The unique electrostatic properties of carbon-bound fluorine, however, may also induce a contrary effect. The conformational restrictions of C -dialkylation seem to be partly dimin-ishable by the electrostatic consequences of fluorination. With this knowledge. 

Finally, it should be noted that the subunits of all citrate synthases are approximately the same size (45 000-50 000) and we have evidence that the hexamers and dimers are functionally similar. Thus, proteolysis studies [92] indicate that the hexameric citrate synthase functions as a trimer of dimers, and by homology modelling to the pig heart enzyme, we have shown that the subunit of the E. coli hexameric protein has a similar conformation to that in the dimeric enzyme. Further catalytic similarities are indicated by site-directed mutageneses [e.g. 93-95]. 

What are the molecular determinants of protein degradations and how do they enter a particular degradation pathway The stability of a protein is thought to be encoded in its primary structure and so is the susceptibility to degradation. For instance, an N-terminal peptide sequence motif, KFERQ, has been identified to target cytosolic proteins for specific lysosomal proteolysis. Studies on protein stability and degradation have established a number of other systematic patterns, notably N-end rule and C-terminal rule. The specific posttranslational modifications may well be considered as programmed events that direct the eventual location of proteins, their functions, and fates. 

Monks, S.A., Gould, A.R., Lumley, P.E., Alewood, P.F., Kern, W.R., Goss, N.H., and Norton, R.S., 1994, Limited Proteolysis Study of Structure-function Relationships in Shi, a Polypeptide Neurotoxin from a Sea Anemone, In Biochim.Biophys.Acta, 1207, 93-101. 

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