Protease protein syntheses

Lamphear, B. J., Kirchweger, R., Skem, T., and Rhoads, R. E. (1995). Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J. Biol. Chem. 270, 21975—21983. 

In normal cells, the GDP/GTP-binding proteins, after protein synthesis, move to the cell membrane to which they become hooked by a hydrophobic farnesyl group. The y-subunit is anchored in the membrane by a post-translational modification of the C-terminal CAAX sequence (C - cystein, AA - aliphatic amino acids, X - methionine). This protein is first enzymatically farnesylated by a specific farnesyltransferase, then the AAX part is cleaved by specific proteases and finally the cystein residue is converted to a methyl ester. 

In A. vinelandii, C-terminal cleavage occurs in crude extracts after restoration of nickel and requires hours rather than minutes, as is the case in vivo. It does not require de novo protein synthesis and surprisingly is not redox or O2 sensitive. Also, it is not inhibited by well-established inhibitors of metallo- or serine protease families (Menon and Robson 1994). 

NUCLEAR MAGNETIC RESONANCE PROTEIN SYNTHESIS INHIBITORS PROTEIN TURNOVER N-END RULE LEUCINE KINETICS PROTEASE La... 

Protein phosphatases 544, 646 Protein S 634 Protein sequenators 118 Protein sequences from genes 119 Protein synthesis 3, 538, 539 Protein tyrosine kinases 544 Protein-disulfide isomerase 83 Protein-DNA interactions 266 Proteinase. See Protease Proteoglycan(s) 181,182. See also Glycosami-noglycans... 

BJ Lamphear, R Yan, F Yang, D Waters, HD Liebig, H Klump, E Kuechler, T Skern, RE Rhoads. Mapping the cleavage site in protein synthesis initiation factor elF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. J Biol Chem 268 19200-19203, 1993. 

Kerekatte, V., Keiper, B.D., Badorff, C., Cai, A., Knowlton, K.U., and Rhoads, R.E. (1999). Cleavage of poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo another mechanism for host protein synthesis shutoff J Virol 73, 709-717. 

HIV-1 Protease as a Paradigm for Elucidating Biological Function by Chemical Protein Synthesis... 

The work on HIV protease demonstrates how chemical protein synthesis allowed isotope labeling of a 22-kDa protein with atomic precision and provided further insights into the chemical basis of the proteolytic cleavage reaction. Isotope labeling with atomic precision has since then been used to reveal structural features of other either chemically synthesized or semisynthetic proteins (27-29). 

There is evidence supporting a role for hepatic damage by intravascular proteases in the pathogenesis of neonatal hepatic disease, as reviewed in the previous edition of this textbook,The AAT deposits in the hepatic endoplasmic reticulum do not bind normally to calnexin, one of the chaperones for protein synthesis and release it is known that proteolytic enzymes reduce the activity of intracellular, membrane-bound proteins involved in metabolic processes. An additional component in congenital and neonatal hepatic disease may be exposure to maternal estrogens, which increase susceptibility to damage from hepatitis viral infections and some toxins. 

The proteasome and other proteases generate free amino acids. Ubiquitinated proteins are processed to peptide fragments from which the ubiquitin is subsequently removed and recycled. The peptide fragments are further digested to yield free amino acids, which can be used for biosynthetic reactions, most notably protein synthesis. Alternatively, the aminO group can be removed and processed to urea (p. 661) and the carbon skeleton can be used to synthesize carbohydrate or fats or used directly as a fuel for cellular respiration. 

Urea, the end product of nitrogen metabolism, accumulates rapidly in ARF. Most patients with ARF have a primary stressful illness that results in ureagenesis, and thus protein breakdown is markedly accelerated. Protein catabolism in ARF may be stimulated as the result of insulin resistance, metabolic acidosis, circulating proteases and inflammatory mediators, and the effects of uremic toxins. The mechanism may be direct, via modulation of protein synthesis, or indirect, by inhibiting the action of anabolic hormones. ... 

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