Proteolytic adaption

To cite an example, this strategy was also used to activate methotrexate-Phe (6.36, R=Phe) and other methotrexate-a-peptides in the vicinity of tumor cells [64], Carboxypeptidase A is normally synthesized as a zymogen that is inactive without proteolytic removal of its propeptide end by trypsin. To adapt this system to GDEPT, a mutant form of the enzyme (CPASX3) was... 

Figure 4 The biosynthesis of nisin A as a representative example of the posttranslational maturation process of lantibiotics. Following ribosomal synthesis, NisB dehydrates serine and threonine residues in the structural region of the prepeptide NisA. NisC subsequently catalyzes intramolecular addition of cysteine residues onto the dehydro amino acids in a stereo- and regioselective manner. Subsequent transport of the final product across the cell membrane by NisT and proteolytic cleavage of the leader sequence by NisP produces the mature lantibiotic. For the sequence of the leader peptide, see Figure 6. Adapted with permission from J. M. Willey W. A. van der Donk, Annu. Rev. Microbiol. 2007, 61, 477-501.

Fig. 17.9. Schematic diagram of MuDPIT proteomics (adapted from Yates, 1998). Protein mixtures of interest are cleaved via proteolytic activity and separated via a series of liquid chromatography separations. Identification of the proteins present relies on sequence tags produced from tandem mass spectrometry. Even low-abundance proteins should be represented at least on one occasion.

Hennessy, J.P. and Siebenaller, J.F. (1987). Pressure-adaptive differences in proteolytic inactivation of M4-lactate dehydrogenase analogues from marine fishes. Journal of Experimental Zoology 241,9-15. 

The metabolic functions of living organisms are maintained by a complex interplay of regulatory networks. Enzymatic activity and gene expression are permanently adapted for an optimum performance and may be completely switched on and off in a reversible manner. Typical mechanisms involved in biological systems include the stimulation and inhibition by control proteins or metabolite molecules, allosteric interactions, proteolytic activation, redox transformations, and reversible covalent bond modifications such as phosphorylation and dephosphorylation (5). 

Adapted from Table 1 in Puente et al. Human and mouse proteases a comparative genomic approach. Nat. Rev. Genet. 4(7) 544-558, 2003 and updated according to Puente et al., A genomic view of the complexity of mammalian proteolytic systems. Biochem Soc Trans. 33... 

It seems reasonable to suppose that the elevated cathepsin activity in dystrophic muscle, by enhancing muscle protein breakdown in vivo, is the cause of the increased rate of protein turnover the increased synthesis could then be seen as an adaptive response to the accelerated breakdown. There is yet, however, no real evidence that this is so the factors which control the breakdown of protein in muscle fibers are probably complex and little understood (PIO). A further possibility, that the proteins of atrophying muscles are in some way more susceptible to breakdown by proteolytic enzymes, seems unlikely Kohn (K9) reported that myosin from denervated rat muscle was digested normally by trypsin, and this was found to be true also of myosin from dystrophic mice and chickens (Kl), whereas Pollack and Bird (P21) stated that the autolytic activity of denervated muscle was not increased relative to the breakdown of hemoglobin by the muscle. 

Figure 18.2 Phylogenetic analysis segregates the human caspases into two major subfamilies, one based on caspase-1 previously referred to as ICE, for interleukin-converting enzyme, and the other based on similarities to the C. elegans cell death gene, ced-3. Further classification of the caspases is possible into those that mediate cytokine maturation that are involved in inflammation, those with a short prodomain involved in the effector phase of apoptosis (shown boxed), and those with a long prodomain that are involved in the initiator phase of apoptosis (not boxed). Note evolutionary distances are not accurately represented in this dendrogram. (Adapted from Nicholson, D.W. (1999). Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 6 1028-1042.)...

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