Ex Parte BORNSCHEUER et al - Page 19




              Appeal No. 2005-1745                                                                                     
              Application No. 09/161,680                                                                               


              change in a reaction catalyzed by an enzyme are the substrates of that enzyme.”                          
              Darnell, p. 55, col. 2, para. 3.7   “Enzyme molecules have two important regions, or sites:              
              one that recognizes and binds the substrate(s), and one that catalyzes the reaction once                 
              the substrate(s) have been bound. . . .  In some enzymes the catalytic site is part of the               
              substrate-binding site.  These two regions are called, collectively, the active site.”  Id., p.          
              56, col. 1, para. 2.  “The specificity of an enzyme is determined by the different rates at              
              which it catalyzes closely similar chemical reactions or by its ability to distinguish                   
              between closely similar substrates.”  Id., para. 1.  With either event, the first step in                
              enzyme catalysis requires the binding of the enzyme to the substrate.  In this regard,                   
              there are two mechanisms of interaction.  One is known as the “lock and key”                             
              mechanism whereby the enzyme and substrate simply fit together forming “a complex                        
              stabilized by a variety of noncovalent bonds.”  Darnell, p. 60, para. 1.  The other                      
              mechanism, known as “induced fit” occurs when                                                            
                     the substrate induces a conformational change in the enzyme that causes the                       
                     catalytic residues to become positioned correctly.  Molecules that attach to the                  
                     substrate-binding site, or recognition site, of the enzyme but that do not induce a               
                     conformational change are not substrates of that enzyme.  Thus an enzyme                          
                     differentiates between a substrate and a nonsubstrate in two ways: Does the                       
                     potential substrate bind to the enzyme?  If so, does it produce a conformational                  
                     change?  When both criteria are met, the enzyme-substrate complex is said to                      
                     demonstrate an induced fit [second emphasis added] Darnell, p. 60, para. 2.                       


                     7 Darnell et al. (Darnell),  Molecular Cell Biology, 2nd Edition, Scientific American             
              Books, distributed by W.H. Freeman and Company, NY, 1990.  Relevant pages                                
              attached.                                                                                                
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