TY - JOUR
T1 - Enzymatic transition state poise and transition state analogues
AU - Schramm, Vern L.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (ANDN or SN2), aromatic nucleophilic displacements (AN*DN or S N-Ar), and both concerted and stepwise dissociative nucleophilic displacements (DNAN and DN*AN; SN1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S N2 or DNAN) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise.
AB - The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (ANDN or SN2), aromatic nucleophilic displacements (AN*DN or S N-Ar), and both concerted and stepwise dissociative nucleophilic displacements (DNAN and DN*AN; SN1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S N2 or DNAN) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise.
UR - http://www.scopus.com/inward/record.url?scp=0041472499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041472499&partnerID=8YFLogxK
U2 - 10.1021/ar0200495
DO - 10.1021/ar0200495
M3 - Review article
C2 - 12924955
AN - SCOPUS:0041472499
SN - 0001-4842
VL - 36
SP - 588
EP - 596
JO - Accounts of Chemical Research
JF - Accounts of Chemical Research
IS - 8
ER -