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Beyond the Molecular Frontier: Challenges for Chemistry and Chemical Engineering (2003)
Board on Chemical Sciences and Technology (BCST)

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112
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Beyond the Molecular Frontier: Challenges for Chemistry and Chemical Engineering

Ribosomes

The nucleotide sequences of the genes encoded in DNA are transcribed into the same sequences of messenger RNA, again carrying the genetic code, and these RNAs direct the synthesis of proteins with defined sequences of amino acids. Protein synthesis occurs in a cellular machine called a ribosome, which takes in messenger RNA and some amino acids linked to transfer RNA and uses base pairing to direct their assembly into a protein. The base pairing occurs because each kind of amino acid is attached to a different transfer RNA, one that carries a code for that particular amino acid. Thus messenger RNA plays the role of template for protein synthesis, and transfer RNA guides the amino acids to the correct spot. Assembling the protein still requires a catalyst to link the amino acids together.

Essentially all biological catalysts in the modern world are themselves proteins, enzymes. However, in 1989 Sidney Altman and Thomas Cech received the Nobel prize in chemistry for showing that RNA itself could act as a catalyst for some biological reactions. This led to the idea that in an earlier time, as life was evolving, RNA may have been both the information molecule (a role usually played by the more stable DNA now) and the catalyst (the role that protein enzymes now play.) Since this idea indicates that in early times the synthesis of proteins was catalyzed by RNA, not by protein enzymes, the intriguing question is whether this is still true today.

Ribosomes are complex structures consisting of one small RNA molecule and two large ones together with some 50 to 60 different proteins. Their general shape had been determined by electron microscopy some years ago, but a major breakthrough occurred in 2000. X-ray diffraction was used to determine the detailed molecular structure of a ribosomal particle that consists of almost all the molecules in a ribosome and exhibits the full catalytic and regulatory functions of a ribosome.3 The trick was to get this large particle, about 100 times as large as a simple protein enzyme, to crystallize so the x-ray technique could be applied. The results are striking, but for the real details it is important to consult the original articles). Such a detailed structure can help medicinal chemists to develop useful drugs that bind to the ribosome, but the more important result has to do with the catalytic center.

The catalytic center of the ribosome, where the protein is actually made, is now seen to consist of RNA, not of a protein enzyme! The many

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N. Ban, P. Nissen, J. Hansen, P. B. Moore, and T. A. Steitz, Science, 289, 905, 2000; P. Nissen, J. Hansen, N. Ban, P. B. Moore, and T. A. Steitz, Science, 289, 920, 2000.

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112