Disease relevance of trpA

• The suppressor allows readthrough of UGA mutations at two positions in trpA and at two sites in bacteriophage T4 [1].
• A new mutant strain of Escherichia coli, strain ICR-47, contains a frame-shift mutation in the trpA gene, the gene most distal to the operator in the trp operon [2].

High impact information on trpA

• The suppressor also does not allow mistranslation of the UGA-related trpA missense mutations UGG at positions 211 and 234, AGA at 211 and 234, CGA at 211, or UGU and UGC at 234 [1].
• However, there was one genetic class of trpA missense mutants, represented by trpA34, for which protein structure analyses failed to detect an amino acid substitution [3].
• Fusion of trpB and trpA of Escherichia coli yields a partially active tryptophan synthetase polypeptide [4].
• The chromosomal order of all bacterial genes that specify tryptophan synthetase beta and alpha chains, respectively, is trpB-trpA [4].
• In vitro mutagenesis and overexpression of the Escherichia coli trpA gene and the partial characterization of the resultant tryptophan synthase mutant alpha-subunits [5].

Biological context of trpA

• A random single base pair saturation mutagenesis procedure (Myers, R.M., Lerman, L.S., and Maniatis, T. (1985) Science 229, 242-247) was applied in vitro to subcloned fragments of the trpA gene, which codes for this polypeptide [5].
• Each type of revertant trpA was cloned and its DNA sequence determined. trpA(UGA211) gave rise to two previously unidentified types of missense revertant [6].
• The mutagenized fragments were subcloned into the plasmid vector and used to transform to ampicillin resistance (Ampr) a recipient strain containing a UGA mutation in trpA [7].
• These studies also revealed an unpredicted flexibility in the primary amino acid sequence of the trpA product, the alpha subunit of tryptophan synthase [8].
• The molecular characterization of the mutation that corrected the Eut- phenotype caused by allele Delta903 showed that the new mutation was a deletion of two nucleotides at the tonB-trpA fusion site [9].

Associations of trpA with chemical compounds

• These trpA fragments were mutagenized in vitro (using nitrous acid, formic acid, hydrazine, and potassium permanganate), and several thousands of mutants have been isolated [5].
• By analyzing reversion patterns of defined trpA alleles, we showed that pKM101 caused all types of spontaneous base-pair substitution mutations with the possible exception of guanine . cytosine leads to adenine. thymine transitions [10].
• Low cysteine content (one in trpB; zero in trpA) is a striking feature of these proteins, which may contribute to their thermostability [11].
• The frequency of reversions induced by one mutagen, methyl methanesulphonate (MMS), increased in proportion to the average number of trpA gene copies per cell, whereas the frequency of reversions induced by the other compounds was dependent on the average number of chromosome replicating forks per cell [12].

References