Isoleucine codons

The target of mupirocin is one of a group of enzymes which couple amino acids to their respective tRNAs for delivery to the ribosome and incorporation into protein. The particular enzyme inhibited by mupirocin is involved in producing isoleucyl-tRNA. The basis for the inhibition is a structural similarity between one end of the mupirocin molecule and isoleucine. Protein synthesis is halted when the ribosome encounters the isoleucine codon through depletion of the pool of isoleucyl-tRNA. 

P. Wang, A. Fichera, K. Kumar, D.A. Tirell, Alternative translations of a single RNA message An identity switch of (2S,3R)-4,4,4-trifluorovaline between valine and isoleucine codons, Angew. Chem. Int. Ed. 43 (2004) 3664-3666. 

Furukawa S, OzaM A, Nakanishi T (1988) L-threonine production by L-aspartate- and L-homoseiine-resistant mutant oiEscherichia coli. Appl Microbiol Biotechnol 29 550-553 Gardner JF (1979) Regulation of the threonine operon tandem threonine and isoleucine codons in the control region and translational control of transcription termination. Proc Natl Acad Sci... 

A striking feature of the genetic code is that an amino acid may be specified by more than one codon, so the code is described as degenerate. This does not suggest that the code is flawed although an amino acid may have two or more codons, each codon specifies only one amino acid. The degeneracy of the code is not uniform. Whereas methionine and tryptophan have single codons, for example, three amino acids (Leu, Ser, Arg) have six codons, five amino acids have four, isoleucine has three, and nine amino acids have two (Table 27-3). 

Table 6.1 shows the relationship between the codon sequence in mRNA and its corresponding amino acid in the new protein. Because there are 64 (43) different anticodon combinations and only 20 encoded amino acids, some different anticodon sequences encode for the same amino acid. Generally, all the anticodons matching a given amino acid will have the same first two nucleotides. Exceptions are arginine, serine, and isoleucine. For example, the codon for proline will always start with CC, but the arginine codon may start with either AG or CG. The 3 end of the tRNA anticodon pairs with the 5 end of the mRNA codon. In other words, the codon and anticodon align and bind in an antiparallel fashion. 

This nine-base strand of m-RNA contains three codons UUC GGC, and, AUU, and calls for the amino acids phenylalanine, glycine, and, isoleucine in that order.7 Thus the order of the bases in DNA dictates a particular sequence in the m-RNA strand. When the m-RNA strand is complete, it leaves the nucleus and heads for the ribosomes in the cytoplasm. 

Few polymorphisms have been detected in the human AHR gene. Thus far only one human AHR polymorphism has been shown to exert a substantial effect on receptor function human AHR that encodes serine at codon 517, when in combination with isoleucine at 570 and lysine at 554 (a presumed haplotype found only in individuals of African descent), fails to sustain CYP1A1 induction in vitro even though this variant is competent to bind the inducer, TCDD, and to bind AH response elements derived from the CYP1A1 gene (80). 

The coding strand of DNA gives the same sequence as the mRNA, except for T being present in the DNA in place of U. Thus, the codon will change from AUA to AUG. This causes isoleucine to be replaced by methionine. 

A surprise was encountered when the sequence of human mitochondrial DNA became known. Human mitochondria read UGA as a codon for tryptophan rather than as a stop signal (Table 5.5). Furthermore, AGA and AGG are read as stop signals rather than as codons for arginine, and AUA is read as a codon for methionine instead of isoleucine. 

AUA and AUU are initiation codons, as is AUG. Both AUA and AUG also code for methionine. AUU also codes for isoleucine, as in the universal code. 

It follows that the array of codons represents the instructions for producing 20 amino acids, the so-called common amino acids. These amino acids are named and symbolized as alanine (Ala), arginine (Arg), asparagine (Asn), aspartate (Asp), cysteine (Cys), glutamine (Gin), glutamate (Glu), glycine (Gly), histamine (His), isoleucine (lie), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Val). 

Viral replication in the presence of indinavir selects for drug-resistant virus. The primary indinavir resistance mutations occur at HIV protease codons 46 (a methioiune-to-isoleucine or leucine), 82, and 84. However, secondary resistance mutations can accumulate at codons 10, 20, 24, 46, 54, 63, 71, 82, 84, and 90, and these are associated with clinical indinavir resistance as well as cross-resistance to other HIV protease inhibitors. 

In patients treated with ritonavir as the sole protease inhibitor, virus replication in the presence of drug selects for drug-resistance mutations. The primary ritonavir resistance mutation is usually at protease codon 82 (several possible substitutions for valine) or codon 84 (isoleucine-to-valine substitution). Additional mutations associated with increasing resistance occur at codons 20, 32, 46, 54, 63, 71, 84, and 90. High-level resistance requires accumulation of multiple mutations. 

All organisms studied so far use the same genetic code, with some rare exceptions. One exception occurs in human mitochondrial mRNA, where UGA codes for tryptophan instead of serving as a stop codon, AUA codes for methionine instead of isoleucine, and CUA codes for threonine instead of leucine. 

Because of the considerations just made, it is of interest to divide amino acids (see Fig. 10.3) into three classes (i) those that only contain G and/or C in the first and second positions of their codons (ii) those that only contain A and/or T and (iii) those that contain G and/or C as well as A and/or T. The GC class comprises four amino acids, alanine, arginine (quartet codons), glycine, and proline the AT class comprises seven amino acids, asparagine, isoleucine, leucine (duet codons), lysine, methionine, phenylala-... 

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