Page 257 - Color Atlas of Biochemistry

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248 Molecular genetics

Amino acid activation tortions of the erythrocytes and disturbances
of O 2 transport (sickle-cell anemia).

A. The genetic code
B. Amino acid activation
Most of the genetic information stored in the
genome codes for the amino acid sequences Some 20 different amino acid tRNA ligases in
of proteins. For these proteins to be ex- thecytoplasm each bind onetypeoftRNA
pressed, a text in “nucleic acid language” (see p. 82) with the corresponding amino
therefore has to be translated into “protein acid. This reaction, known as amino acid acti-
language.” This is the origin of the use of the vation, is endergonic and is therefore coupled
term translation to describe protein biosyn- to ATP cleavage in two steps.
thesis. The dictionary used for the translation First, the amino acid is bound by the en-
is the genetic code. zymeand reacts therewith ATP to form di-
As there are 20 proteinogenic amino acids phosphate and an “energy–rich” mixed acid
(see p. 60), the nucleic acid language has to anhydride (aminoacyl adenylate). In the sec-
contain at least as many words (codons). ond step, the 3 -OH group (in other ligases it
However, there are only four letters in the is the 2 -OH group) of the terminal ribose
nucleic acid alphabet (A, G, C, and U or T). To residue of the tRNA takes over the amino
obtain 20 different words from these, each acid residue from the aminoacyl adenylate.
word has to be at least three letters long In aminoacyl tRNAs, the carboxyl group of
(with two letters, there would only be the amino acid is therefore esterified with
2
4 =16 possibilities). And in fact the codons theriboseresidue of theterminaladenosine
do consist of three sequential bases (triplets). of thesequence...CCA-3 .
Figure 1 shows the standard code in “DNA The accuracy of translation primarily de-
language” (i. e., as a sequence of triplets in the pends on the specificity of the amino acid
sense strand of DNA, read in the 5 3 direc- tRNA ligases, as incorrectly incorporated
tion; see p. 84), represented as a circular dia- amino acid residues are not recognized by
gram. The scheme is read from the inside to theribosomelater. A “proofreading mecha-
the outside. For example, the triplet CATcodes nism” in the active center of the ligase there-
for the amino acid histidine. With the excep- fore ensures that incorrectly incorporated
tion of the exchange of U for T, the DNA co- amino acid residues are immediately re-
dons are identical to those of mRNA. moved again. On average, an error only occurs
3
As thegeneticcodeprovides 4 =64 co- once every 1300 amino acid residues. This is a
dons for the 20 amino acids, there are several surprisingly low rate considering how similar
synonymous codons for most amino acids— some amino acids are—e. g., leucine and iso-
thecodeis degenerate. Three triplets do not leucine.
code for amino acids, but instead signal the
end of translation (stop codons).Another
special codon, the start codon,marks thestart C. Asp–tRNA ligase (dimer)
of translation. The code shown here is almost Theillustration shows theligaseresponsible
universally applicable; only the mitochondria for the activation of aspartate. Each subunit of
(see p. 210) and a few microorganisms devi- the dimeric enzyme (protein parts shown in
ate from it slightly. orange) binds one molecule of tRNA Asp (blue).
As an example of the way in which the Theactivecenters can belocated by the
code is read, Fig. 2 shows small sections boundATP (green). They areassociatedwith
from the normal and a mutated form of the the 3 end of the tRNA. Another domain in the
β-globin gene (see p. 280), as well as the cor- protein (upper left) is responsible for “recog-
responding mRNA and protein sequences. The nition” of the tRNA anticodon.
point mutation shown, which is relatively fre-
quent, leads to replacement of a glutamate
residue in position 6 of the β-chain by valine
(GAG GTG). As a consequence, the mutated
hemoglobin tends to aggregate in the deoxy-
genated form. This leads to sickle-shaped dis-

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