Posttranslational proteins

Fig. 1 Relationship of posttranslational protein isoprenylation pathways to the mevalonate pathway of cholesterol biosynthesis...

Although it is true that abnormal proteins increase with age, most of them are a result of posttranslational changes. An example is the various isoforms of creatine kinase (CK). Here, the major isoenzyme, CK-MM (isoform CK-33), is normally synthesized in the heart and skeletal muscle. However, after its release into the circulation, carboxypeptidase hydrolyzes the terminal lysine from one of the M-peptides to form CK-32. Subsequent hydrolysis of the terminal lysine from the second M-peptide produces the third isoform, CK-3i (W8). Numerous similar posttranslational proteins are produced. Hence, the presence of abnormal proteins per se does not support this aging theory. 

Posttranslational Protein Modification a mechanism of biological control of protein activity by covalent modification after protein synthesis... 

Rucker RB, Wold E. Cofactors in and as posttranslational protein modifications. EASEB J. 1988 2 2252-2261. 

Protein kinases and protein phosphatases catalyze phosphorylation and dephosphorylation of cellular proteins. Posttranslational protein phosphorylation is a major mechanism of signal transduction in eukaryotes it serves as a reversible switch that alters the activity of target proteins as a means to link stimuli to the appropriate cellular response. In this article,... 

Chemical tools have played a central role in elucidating the function of posttranslational protein phosphorylation. Kinase and phosphatase inhibitors have played a major role in the study of protein phosphorylation because they allow rapid, reversible inactivation of the target in meaningful contexts (cells and organisms) to study its biologic function. Chemical tools have also helped identify the direct substrates of individual kinases and phosphatases, and conversely, they have helped identify which kinase is responsible for phosphorylating a particular phosphoprotein. Here I will focus on chemical tools developed for protein kinases several reviews discuss chemical tools for protein phosphatases (15, 16). 

In eukaryotic systems, challenges intrinsic to NMR (e.g., low sensitivity or proper discrimination between target and background signals) become even more pronounced. Interesting applications of NMR to eukaryotic systems are developing that study important cellular features like posttranslational protein modification or directed transport that are not observed in prokaryotic cells (150). 

The presence of a nitrogen-containing side chain facilitates interaction with the catalytic site of FPPS, an enzyme in the metabolic pathway that is required for the production of the isoprenoid hpids farnesyl diphosphate and geranylgeranyl diphosphate, essential metabolites for posttranslational protein prenylation [5, 8]. Inhibiting the prenylation of guanosine triphosphate-binding proteins such as Ras, Rho, and Rac disrupts the normal cellular signal transduction that is required for osteoclast function and survival [5]. 

The incorporation of new functional groups can also be accomplished using the metabolic machinery for posttranslational protein modifications. These methods rely on the ability of some modification enzymes to process and install analogs of their natural substrates containing reactive handles of interest. In an early demonstration of this technique, it was shown that derivatives of N-acetylmannosamine 40a bearing ketones 40b) [62] or azides 40c [63] in the acyl moiety are tolerated by enzymatic pathways that produce sialic acid. By feeding these unnatural building blocks to cell cultures,... 

Biosynthesis of Other Acylated Glycerophospholipids (Figure 19.8) Posttranslational Protein Modification by Lipids (Figure 19.9)... 

Eichler J, Adams M W (2005). Posttranslational protein modification in Archaea. Microbiol. Mol. Biol. Rev. 69 393-425. 

Poly(ADP-ribosyl)ation is a posttranslational protein modification carried out by a family of enzymes, referred to as poly(ADP-ribose) polymerases (PARPs). The biochemistry of poly(ADP-ribose) formation and degradation, and the molecular and cell biolc of the enzymes involved are described in detail in several other Chapters. However, it is worth summarizing several facts that are particularly relevant for the link between pol)r(ADP-ribosyl)ation and aging. 

MASS SPECTROMETRY-BASED METHODS TO INVESTIGATE POSTTRANSLATIONAL PROTEIN MODIFICATIONS BY LIPID PEROXIDATION PRODUCTS... 

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