Point mutations protein synthesis

Protein design by site-directed mutagenesis on pyruvate decarboxylase became possible after the 3D-structure of the enzyme from Saccharomyces uvarum had become available [35], Based on sequence comparison and secondary structure prediction, the 3D-structure of the yeast enzyme served as a model for PDCZ.m. [163], The point mutations which have been introduced into the two enzymes (Tables 4 and 5) concern catalytically important residues as well as significant side-chain interactions at the domain interface of the dimer. Besides, site-directed mutagenesis offered a powerful tool to improve the car-boligase reaction of PDCZ.m. with respect to the synthesis of (P)-PAC [163,164,170]. 

Linezolid inhibits protein synthesis by binding to the P site of the 508 ribosomal subunit and preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis. As mentioned above, there is no crossresistance with other drug classes. Resistance in enterococci and staphylococci is due to point mutations of the 238 rRNA. As multiple copies of 238 rRNA genes are present in bacteria, resistance generally requires mutations in two or more copies. 

The genetic mutations are mainly deletions, but insertions or duphcations also occur, as well as missense and nonsense point mutations (see Fig. 34.20). Four classes of mutations have been identified. The first class involves null alleles that either direct the synthesis of no protein at all or a protein that cannot be precipitated by antibodies to the LDL receptor. In the second class, the alleles encode proteins, but they cannot be transported to the cell surface. The third class of mutant alleles encodes proteins that reach the cell surface but cannot bind LDL normally. Finally, the fourth class encodes proteins that reach the surface and bind LDL but fail to cluster and internalize the LDL particles. The result of each of these mutations is that blood levels of LDL are elevated because cells cannot take up these particles at a normal rate. 

Y766F <60> (<60>, the Y766F FGF receptor mutant is unable to associate with tyrosine-phosphorylate PLC y or to stimulate hydrolysis of phosphati-dylinositol. Nevertheless, the Y766F FGF receptor mutant can be autophos-phorylated, and can phosphorylate several cellular proteins and stimulate DNA synthesis [191] <60>, fibroblast growth factor receptor with the single point mutation fails to associate with PLC y in response to FGF. The mutant... 

The anticodon may either correspond to a triplet sequence normally involved in dictating the position of a given amino acid, or it is a modulating triplet, which facilitates the disconnection of the ribosome from the messenger. Thus, the chances for a ribosome to fall off its mRNA increase as the distance between the reading point and the operator increases. The position of the cistron within the polycistronic operon and the existence of modulating triplets could well explain the modulation of protein synthesis, or rate at which different proteins are synthesized. When the polarity is modified as a result of a mutation, it is assumed that a coding triplet is replaced by a modulation triplet. 

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