Proteins proteolytic processing

Missense mutations in the Notch3 gene cause CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lenkoencephalopathy). Notch is a type I integral membrane protein proteolytically processed in its extracellular domain by fnrin and the metalloproteinase knzbanian. The signal transduction cascade... 

Wischik, C. M. Horsley, D. Rickard, J. E. Harrington, C. R. Drug screening for effectors of tau protein proteolytic processing and expression systems of controlled aggregation in treatment of neurodegenerative disease. PCT Int. Appl. WO 2002055720, 2002 Chem. Abstr. 2002,137, 88474. 

Aeromonas hydrophila is a bacterium that causes diarrheal diseases and deep wound infections. These complications arise due to pore formation in sensitive cells by the protein toxin aerolysin. Proteolytic processing of the 52-kD precursor proaerolysin (Figure 10.34) produces the toxic form of the protein, aerolysin. Like a-hemolysin, aerolysin monomers associate to form a heptameric transmembrane pore. Michael Parker and coworkers have proposed... 

In mammalia, seven different members encoded by distinct genes have been identified, all of which are activated by a distinct set of cytokines. Diversity in signaling is provided by variants of STAT proteins derived from either alternative splicing of RNA transcripts or proteolytic processing (e.g., STATs 1,3,4, and 5) and the ability of certain STATs to form both homodimers and heterodimers with each other. In response to inteiferon-y monomeric STAT1 dimerizes, while upon interferon-a stimulation a heterotrimeric complex consisting of STAT 1 and STAT2 with associated... 

Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. The process is called peptide cleavage, a common mechanism of activation or inactivation of enzymes. They use a molecule of water for this, and are thus classified as hydrolases. 

CarriUo A, Stewart KD, Sham HL, Norbeck DW, Kohlbrenner WE, Leonard JM, Kempf DJ, Molla A (1998) In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. J Virol 72 7532-7541 Chambers TJ, Nestorowicz A, Amberg SM, Rice CM (1993) Mutagenesis of the yellow fever virus NS2B protein effects on proteolytic processing, NS2B-NS3 complex formation, and viral replication. J Virol 67 6797-6807... 

Affect proteolytic processing of precursor proteins to smaller products... 

Blobel, G., and Dobberstein, B. (1975a). Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J. Cell Biol. 67, 835—851. 

Proteolytic processing Various proteins become biologically active only upon their proteolytic cleavage (e.g. some blood factors)... 

Alzheimer s disease, Parkinson s disease, Huntington s disease and amyotrophic lateral sclerosis (ALS) are four prominent fatal neurodegenerative disorders that involve the death of specific populations of neurons (see details in respective chapters). Studies of patients and animal and culture models have provided considerable insight in the cellular and molecular mechanisms responsible for synaptic dysfunction and neuronal degeneration in each disorder [18], In Alzheimer s disease, abnormalities in proteolytic processing of the amyloid precursor protein, due to gene... 

It has long been known that peptides of bacterial origin, such as N-formylat-ed oligopeptides, are potent activators of neutrophils. Bacterial protein biosynthesis is initiated by the codon AUG, which codes for polypeptide chains at the NH2 terminus to start with N-formylmethionine. However, very few mature bacterial proteins actually have this amino acid at the NH2 terminus because Af-formylmethionine is cleaved off by proteolytic processing. Sometimes just this amino acid is cleaved, but often several adjacent residues are also removed with it. These observations formed the basis for the chemical synthesis of a variety of N-formylated oligopeptides and an assessment of their ability to activate neutrophils in vitro. The most potent of these formylated peptides is TV-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). 

Product variants can also be the result of action of cellular proteins on the drug molecule, such as proteolytic processing inside and outside cells. Enzymes from the host cell can make modifications of the product protein. 

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