Protein fidelity

THE FIDELITY FREQUENCY OF TRANSCRIPTION IS CONTROLLED BY PROTEINS BOUND TO CERTAIN DNA SEQUENCES... 

Recent studies have concentrated on control mechanisms, such as the crucial part played by cyclin dependent protein kinases in triggering chromosome duplication and segregation (Nurse 1990) and surveillance mechanisms (checkpoints) that monitor the fidelity of these two processes (Hartwell Weinert 1989). This focus on control is however a recent phenomenon. Earlier studies, largely... 

Again, we are reminded that Nature provides the ultimate model for emulation in the use of cooperative interactions of an enormous number of small structural components through many weak, reversible attractions and repulsions to produce such complex microstructures as proteins, enzymes, viruses, and cells with virtually perfect fidelity (Whitesides, 1991). One important strategy for producing ultra-thin films of promise for microelectronics... 

Nickel chloride has been reported to induce DNA strand breaks in CHO cells [435] in a concentration, which did not significantly injure normal cellular division, and DNA-protein cross-links, which were concentration- and time-dependent and preferentially occurred in cells in the late S phase of the cell cycle [436], The nickel cross-linked proteins included nonhistone chromatin proteins, nonhistone DNA-binding proteins and a 30 kDa protein that comigrated electrophoretically with histone HI. Moreover, blocking of cell growth in S phase [249] and induction of DNA repair synthesis in CHO cells [437] and reduction in the fidelity of DNA synthesis [438, 439], have been reported. 

To date, most approved protein-based drugs are for therapeutic or replacement therapies. They are recombinant versions of natural proteins such as insulin and erythropoietin. Their characteristics and functions are relatively well defined and known. The next phase of biopharmaceuticals, such as antibodies and vaccines, is more complex and requires more tests and characterizations. Controls for the reliability, contamination, and fidelity of expression systems will be high on the agenda in the coming decade. 

Aminoacyl-tRNA synthetases charge the appropriate tRNA with the correct amino acid, which is important in maintaining the fidelity of protein translation. To genetically encode an unnatural amino acid, the substrate specificity of the orthogonal synthetase needs to be altered to charge the orthogonal tRNA with only the desired unnatural amino acid and none of the common 20 amino acids. A general scheme was developed for... 

Protein polymers based on Lys-25 were prepared by recombinant DNA (rDNA) technology and bacterial protein expression. The main advantage of this approach is the ability to directly produce high molecular weight polypeptides of exact amino acid sequence with high fidelity as required for this investigation. In contrast to conventional polymer synthesis, protein biosynthesis proceeds with near-absolute control of macromolecular architecture, i.e., size, composition, sequence, topology, and stereochemistry. Biosynthetic polyfa-amino acids) can be considered as model uniform polymers and may possess unique structures and, hence, materials properties, as a consequence of their sequence specificity [11]. Protein biosynthesis affords an opportunity to completely specify the primary structure of the polypeptide repeat and analyze the effect of sequence and structural uniformity on the properties of the protein network. 

Fung, E.T., Thulasiraman, V., Weinberger, S.R., and Dalmasso, E.A., Protein biochips for differential profiling, Curr. Opinion Biotechnol., 12, 65-69, 2001. Garland, P.B. and Serafinowski, P.J., Effects of stray light on the fidelity of photo-directed oligonucleotide array synthesism Nucleic Acid Res., 30(19), 1-9, 2002. 

Proteins are synthesized by the ribosomal assembly in living organisms, details of which have been the subject of excellent recent reviews. The ribosome is a marvelously complex system of three large RNA molecules and over 50 proteins. This assembly translates the information from mRNA into protein sequence with a fidelity of one mistake per each 10" elongation cycles. ... 

That aminoglycoside binding interferes with translation has been known for at least four decades. The mode of action of these antibiotics decreases the fidelity of translation, such that the organism biosynthesizes proteins that are defective. The presence of defective or nonfunctional proteins leads to the demise of bacteria. Consequently, paromomycin s bactericidal mode of action may come from its ability to lock the A-site into a conformation in which discrimination of cognate and near cognate tRNA is significantly diminished. 

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