_ ' ~  .
1993 PROGRAM Nineteenth Annual
Symposium on
A.M. P.M. C] O t
9:00 Registration and Coffee - Room 137, 12:15 Buffet Lunch. Faculty Club. (Please return 6 mls I S
Chemistry-Physics Building card by April 1. 1993 for reservations. Cost
$8.00 to be paid at registration.) &
9:30 Welcome by Dr. Lee Magid, Vice President
for Research and Graduate Studies, 1:40 Dr. Perry A. Frey, University of Wisconsin-
University of Kentucky - Room 139. Madison
Chemistry-Physics Building Substrate Binding and Catalysis by UDP- o 6 cu ar
Galactose 4-Epimerase
9:40 Introductory Remarks - Tina Amyes, 0
University of Kentucky The most important problem in mechanistic enzy B10 0
mology is the elucidation of how enzymes use the sub-
9:45 Dr. William P. Jencks, Brandeis University strate binding process to enhance the rates of reactions.
Sources of the Catalytic Activity oszymes The question of how UDP-galactose 4epimerase uses
binding interactions to nonreacting portions ot'the sub ,
Enzymes have the ability to increase reaction rates strate to catalyze hydride transfer from the substrate to
by factors of 10 or more for their specific substrates. A the cofactor. NAD, will be presented. The results of
small fraction of this catalysis can usually be accounted kinetic measurements. NMR and Raman spectroscopy. V, , . ,1 .,
for by wellunderstood chemistry. such as nucleophilic and xray ciystallography will be fused into a coherent f , '  .
catalysis and acid or base catalysis by proton donors and hypothesis that explains how the enzyme uses binding . , .. '15 J ,
acceptors at the active site.The source ofthegreaterpart interactions to the uridine 5'diphosphoryl moiety of , .
of the observed catalysis is obscure. but it is clear that substrates to enhance the intrinsic. chemical reactivity of ' ' g " .
much of this catalysis arises from noncovalent interac- NAD at the active site. The simplest interpretation ofthe _ / _
tions 'of the substratets) with the active site. Strain, resultswillbeshown to indicate that the enzyme reduces ' ' '
distortion and desolvation in the enzymesubstratecom the energy of activation for hydnde transfer in part by
plex can decrease the activation energy for reaction but electronically destabilizing the nicotinamide ring ofNAD. _ .
require the expenditure of a large amount of binding established In the memory Of
energy. Attraction ofourlimited knowledge ofthe mecha-~ 2:40 Discussion Anna S. Naff
nisnis 01 how catalySis of chemical reactions and oi
movement is mediated will be reviewed. 2:50 Dr. Gregory A. Petsko, Brandeis University
The Structural Enzymology of Proton- '
10:45 Discussion Transfer Reactions ENZYME CATALYSIS -
10:55 Dr. Stephen J. Benkovic. The Pennsylvania The simplest chemical transformations in inetabo- MEC SM S RUC U
State University . lisni are the proton transfer reactions exemplified by LG AND DESIGN
Catalytic Antibodies certain isomerases and racemases. We have been study- 3 in
mg three such enzymes to understand the structural +03) 8
The field of catalytic antibodies continues to envelop features that lead to efficient proton transfer All ofthese a g ('0
different reaction types and with particularemphasis on enzymes face the common problem of abstracting a a) :5 O SPEAKERS
the. stereochemical-controlof the course of thereaction: hydrogen from a carbon acid ofhigh pKJ with an enzymic 5 E 8 Stephen J, BCIlkOViC
I Will locus on two issues: 1] the mechanism of action ol base of low pK". We have used X-ray crystallography. H QM) sf
several ofthese antibodies and ii) methods for improving sitedirected mutagenesis. and moleculardynamics simu- 0 2H E P61 I 5 A- Frey
their catalytic efficiency. Mechanistic analysis based on lations to arrive at a set ofprinciples for optimal catalysis E5 0 ' William P. Jencks
structure rcactivity correlations, pre and steadystate of this simple reaction. 0) 3 c: .
kinetics. and other reaction probes suggests that the E E 8 Gregory A' PCtSkO
most effective antibodies possess segments of the cata 3:50 Discussion 3 g ED
lytic processes found in enzymes. Efforts to further Q 'F 52 .
improve upon the active site framework or to integrate 4:00 Mixer - Room 137. Chemistry-Physics a 5 3 Monday Aprll 5 1993
additional functions into the antibody binding site through Building
mutagenesis and combinatorial libraries will be de .
scribed E Department of Chemistry
University of Kentucky
55 D555 Lexington, Kentucky 405060055