From Genes to Enzymes, a Chemical Basis for Evolution of Function

Friday February 22
11:35

From Genes to Enzymes, a Chemical Basis for Evolution of Function

Dale Poulter, Bioorganic Chemistry (USA)
Virtually all of the organic molecules required to support life are the products of biosynthe- sis.  The enzymes that catalyze the individual reactions in biosynthetic pathways are typically highly evolved to efficiently synthesize a single stereochemically defined product.  Recent ad- vances in genomics and X- ray crystallography have revealed similarities among the struc- tures of biosynthetic enzymes that allow many of them to be grouped into families whose individual members apparently evolved from a common ancestor.  Over time, similarities at the amino acid level become indistinct and only elements of the three-dimensional structure of the proteins remain to identify members of an extended “superfamily”.  These changes permit enzymes to acquire the ability to synthesize different molecules.  At present it is difficult to predict the function of an enzyme from its gene or its crystal structure without a closely related 
family member whose function is known or supporting chemical evidence.
Highly evolved enzymes, which synthesize a single with high efficiency, can hide important clues the reactions they catalyze.  By perturb- ing the conditions for an enzyme-catalyzed reaction or slightly altering the structure of the enzyme can lead to the appearance of the range of products characteristic of the un- catalyzed reaction.  These new products from closely related reactions provide important clues about how enzymes within a superfamily have evolved and help identify the functions of members within a superfamily.  Examples of how nature has exploited the inherent chemical behavior of isoprenoid substrates to catalyze synthesis of new molecules will be discussed
 
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