Valine codons

Simplicity argues that the genetic blueprint specifying amino acid sequences in proteins should consist of consecutive, nonoverlapping triplets. This assumption turned out to be correct, as is illustrated by the DNA sequence for a gene shown in Fig. 5-5. In addition to the codons that determine the sequence of amino acids in the protein, there are stop codons that tell the ribosomal machinery when to terminate the polypeptide chain. One methionine codon serves as an initiation codon that marks the beginning of a polypeptide sequence. One of the valine codons sometimes functions in the same way. 

The significant structural results which have been discussed here are summarized in Figure 11. All, in the absence of intermolecular solid state effects, fall in a narrow torsional range centered near x= 100° which is quite different from that found in the natural systems. It is apparent that incorporation of a nucleoside in this conformation into a polynucleotide could have dramatic effects on the coding and base-pairing properties of the nucleic acids. Such a result could explain the observation that replacement of a natural pyrimidine nucleoside in the valine codon by 6-AUD or 6-ACD results in a nonfunctional unit [3], and could also explain the anti-neoplastic properties of these and similar molecules. 

The abbreviations for the amino acids are standard. The first, second and third nucleotides for each codon are as indicated. The Methionine codon AUO and Valine codon GUO also stand for initiator codons. The codons UAG, UAA and UGA stand for termination signab. 

Sickle cell anemia (MIM 141900) Sequence of codon 6 of the p chain changed from GAG in the normal gene to GTG in the sickle cell gene, resulting in substitution of valine for glutamic acid... 

Sickle cell disease is caused by a mutation that results in the substitution of a valine residue for a glutamate residue in the sixth position of the hemoglobin P-chain. This results from the substitution of a T for an A in the glutamate codon. When (1) DNA from a patient... 

X can be any of the four nucleobases—G, A, C or U thus, four anticodons can be formed GGC, GAC, GCC and GUC. The antiparallel structure contains the codons GCC, GUC, GGC and GAC. Today, these codons code for the four amino acids alanine, glycine, valine and aspartic acid. These are, astonishingly, the four protein building blocks produced in the best yields in the Miller-Urey experiment, and they... 

RFLP analysis of the p-globin gene for genetic testing has been replaced, by PCR In combination with ASO probes on dot blots. The blot shown here corresponds to the family whose pedigree is shown in Figure T7-9. In the mutant allele, glutamate (E) at codon 6 is replaced by valine (V). 

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. 

For most polypeptide chains initiation begins with one of the three initiation codons, most commonly the methionine codon AUG. When properly placed in an mRNA chain, GUG may also serve as a bacterial initiation codon. In such cases, it codes for methionine rather than for valine. Occasionally UUG, AUU, ACG, and perhaps other codons can initiate translation 288/289 This is less frequent in eukaryotes than in bacteria. The sequence of bases preceding the initiation codon must also be important for recognition of the "start" signal. 

As we have indicated, the codon AUG is the only one generally used to specify methionine, but it serves a dual function in that it is also used to initiate translation. Occasionally, GUG and UUG are also read as an initiating codon in bacteria, but in internal positions these codons are always read as valine and leucine, respectively. In eukaryotes, initiation at codons other than AUG is much less frequent than in prokaryotes. Weak initiation occasionally occurs at GUG, CUG, and ACG codons in eukaryotic systems. The UGA triplet also serves a dual function it is usually recognized as a stop, but on occasion it serves as a codon for selenocys-teine (box 29A). 

Table 27.4 in the text lists the messenger RNA codons for the various amino acids. The codons for valine and for glutamic acid are ... 

As can be seen, the codons for glutamic acid (GAA and GAG) are very similar to two of the codons (GUA and GUG) for valine. Replacement of adenine in the glutamic acid codons by uracil causes valine to be incorporated into hemoglobin instead of glutamic acid and is responsible for the sickle cell trait. 

Codons that specify the same amino acid are called synonyms. Most synonyms differ only in the third base of the codon for example GUU, GUC, GUA and GUG all code for valine. During protein synthesis, each codon is recognized by a triplet of bases, called an anticodon, in a specific tRNA molecule (see Topics G10 and H2). Each base in the codon base pairs with its complementary base in the anticodon. However, the pairing of the third base of a codon is less stringent than for the first two bases (i.e. there is some wobble base-pairing ) so that in some cases a single tRNA may base-pair with more than one codon. For example, phenylalanine tRNA, which has the anticodon GAA, recognizes both of the codons UUU and UUC. The third position of the codon is therefore also called the wobble position. 

This stands for chain initiation and indicates that the codon for methionine (AUG) defines the beginning of the translated portion of an mRNA i.e., methionine is the first amino acid to be incorporated into a polypeptide chain. Less frequently GUG, normally for valine, can function in place of AUG as the chain-initiation codon incorporating methionine (see Table 17.1). It should be noted that while the first amino acid of a newly synthesized polypeptide chain is always methionine (or valine), methionine and valine may also occur within a polypeptide chain. 

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