Structure substrate-assisted catalysis

A structural anomaly in subtilisin has functional consequences Transition-state stabilization in subtilisin is dissected by protein engineering Catalysis occurs without a catalytic triad Substrate molecules provide catalytic groups in substrate-assisted catalysis Conclusion Selected readings... 

Further, for antibody catalysis the methyl ester is too small to be an effective epitope but the participation could be induced if an antibody were able to recruit cocaine from the chair conformation to the less stable boat form (see Fig. 4 for the structure) and reorient the syn-protonated amine and benzoyl ester into proximity. Antibodies can provide significant binding energy and in principle antibody binding could effect conformer selection and promotion of substrate-assisted catalysis. To examine this idea, a detailed computational analysis [89] of the energetics of this reaction was also performed for design of novel TSA structures for the alkaline hydrolysis of boat cocaine in comparison with the hydrolysis of chair cocaine. 

Deoxyribozymes (also called DNA enzymes or DNAzymes) are specific sequences of DNA that have catalytic activity. All currently known deoxyribozymes have been identified by in vitro selection from large random-sequence DNA pools (Joyce, 2004 Silverman, 2009). The catalytic range of DNA encompasses both oligonucleotide and nonoligonucleotide substrates (Baum and Silverman, 2008 Silverman, 2008). This report focuses on deoxyribozymes that are useful for reactions of RNA substrates, especially to assist studies of RNA structure, folding, and catalysis. 

Why is 1F7 10 -times iess active than chorismate mutase The antibody molecule s distinctive architecture does not appear to impose intrinsic structural limitations on catalysis. Indeed, comparison of the active sites of the antibody and the monofunctional enzyme from Bacillus subtilis [26] suggests that the differences between them are more a matter of degree than of kind. Upon complex formation, the hapten is buried to a similar extent in both proteins, and similar types of interactions are available for orienting the flexible substrate correctly for reaction. Furthermore, the enzyme and the antibody seem to promote the rearrangement of chorismate via the same concerted transition state as the uncatalyzed reaction. Other formal mechanistic possibilities, such as a two-step heterolytic process assisted by an enzymic nucleophile, can be ruled out by the lack of appropriate functional groups in the respective active sites [25,26]. 

Examination of protein structure in solution by nuclear magnetic resonance spectroscopy has revealed that a significant amount of internal motion exists in a protein on a timescale of 1 to 10 ns. Such internal motion could transmit kinetic energy from a distant part of the protein to the active site to assist in catalysis. It has been proposed that dynamic fluctations in the protein structure are used by enzymes to organize the enzyme-substrate complex into a reactive conformation. 

Enzymes are proteins that catalyze reactions necessary to sustain life. Like other proteins, enzymes consist of chains of amino acids. The structural formulas of a few important amino acids are shown in Figure 29F-1. Molecules formed by linking two or more amino acids are called peptides. Each amino acid in a jjeptide is called a residue. Molecules with many amino acid linkages are polypeptides, and those with long polypeptide chains are proteins. Enzymes differ from other proteins in that a specific area of the structure, called the active site, assists in the catalysis. As a result, enzyme catalysis is often quite specific, favoring a particular substrate over other closely related compounds. 

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