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Chapter 11 Structure and Function of Ribozymes Outline Definition and Discovery of Ribozymes Comparison between Protein-based and RNA-based Enzymes Types of ribozymes Small ribozymes Large ribozymes Mechanism of Ribozyme Catalysis Mechanism of small ribozyme catalysis Mechanism of large ribozyme catalysis Significance of the discovery of ribozymes and its applications (self-study) Discovered by Tom Cech and Sydney Altman (the Nobel prize laureates) Ribozymes just are catalytic RNA molecules, which can catalyze a number of the chemical reactions Ribozymes can be naturally-occurring or artificially-made Two naturally-occurring ribozymes are present in almost every organism: RNase P and Ribosome Cech Altman Discovery and Definition of Ribozymes ribozyme rate enhancements can be substantial. For example, the rate constant for chemistry of the self-cleaving HDV ribozyme is estimated at 102–104 s–1, which is close to the maximal cleavage rate of RNase A. ribozymes can use cofactors during catalysis, and they can be switched on and off by the binding of small-molecule allosteric effectors. ribozymes, like protein catalysts, fold into specific 3D shapes that can harbor deep grooves and solvent-inaccessible active sites. These tertiary structures facilitate catalysis in part by orienting substrates adjacent to catalytic groups and metal ions. To facilitate chemical transformations, catalysts stabilize the transition state. Both protein and RNA catalysts may achieve this by adding or removing protons during a reaction, orienting substrates so that they are optimally positioned to react, and using binding interactions away from the reaction site to ‘force’ an unfavorable contact that is relieved in the transition state. Common points between Protein-based and RNA-based Enzymes Proteins and RNA are very different polymers. The phosphodiester backbone of nucleic acids is charged, and thus RNA has a large electrostatic component in which metal ion
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