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Current Genomic Research: The Proteins Have It
Pages 54-61

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From page 54...
... A single nucleotide base change in the chromosomal DNA that results in a single amino acid change in a single protein can have devastating, if not fatal, consequences for an individual organism and his or her offspring. Sickle cell anemia, in which the protein hemoglobin forms long aggregates that dramatically reduce its oxygen-carrying capacity and give rise to the characteristic sickling distortion of red blood cells, is a consequence of a mutation of a single amino acid from the negatively charged aspartic acid to the aliphatic valine.
From page 55...
... Protein structure can be classified in a hierarchical fashion (Figure 1~. The first level is the amino acid sequence or "primary structure," and the next is the "secondary structure," which is the regular repetition of backbone dihedral angles in a linear stretch of amino acids that gives rise to a common structural unit.
From page 56...
... 56 ENGINEERING CHAEEENGES AND OPPORTUNITIES IN THE GENOMIC ERA FIGURE 1 The hierarchical nature of protein structure. SOURCE: Reprinted with permission of Wadsworth, an imprint of the Wadsworth Group, a division of Thomson Learning (Boyer, 1999~.
From page 57...
... SOURCE: Department of Biochemistry and Molecular Biology, University College, London. This figure can be viewed in color at .
From page 58...
... It was first pointed out by Chothia and Lesk (1986) that there is a direct and predictable relationship between the percent sequence identity of two proteins and the backbone root mean square deviation of the two structures.
From page 59...
... This distribution, which is similar in other organisms, provides an illustration of the scale of missing "fold space." Filling in these missing structures via a number of different strategies is a goal of current genomics research. This information is important not only because it provides fundamental insights into how different protein folds can be used for the same or different functions but also because it is of practical importance in drug design.
From page 60...
... Purification of large quantities of protein to a reasonable level of purity can be accomplished quite readily by attaching a universal "tag," which allows all proteins to be purified by that same method, regardless of their individual chemical nature. Development of an additional universally applicable purification step, which would easily allow proteins to be purified to the high levels required for crystallization, is important.
From page 61...
... I acknowledge Christine Orenga and Janet Thornton for the CATH protein classification system and for the illustrations in this article that are taken from their work. REFERENCES Balasubramanian, S., T


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