I" C D
e 2. e
5' 5 2 Fourth Annual Symposium on
8:30 Coffee-CP Room 137 0'3 3 S
0 5'
9:00 Welcome and Introduction  CP Room 139 .5 3 g
7 -h 0
9:15 INTRODUCTION-REGULATION OF ENZYME .< 5 3
ACTIVITY 4; a g
 Dr. W. N. Lipscomb  8 g 3
C) 7? 
9:30 INDUCED FIT AND ALLOSTERIC INTERAC- 0< 5* c H E M I S T R Y
TIONS IN THE STRUCTURE AND FUNCTION
OF YEAST HEXOKINASE a n d
 Dr.T. A. Steitz 
High resolution structures of monomeric and dimeric M O L E C U L A R
yeast hexokinase and their substrate complexes pro-
vide important clues to the specificity and mechanism
of this kinase and suggest models for its activation. B I O L o G Y
The binding of glucose results in a dramatic structural
change; one domain of the monomer (40% of the
atoms) rotates 12 relative to the other domain, there-
by closing off the deep cleft into which the sugar established in memory Of
binds. The energy for this induced fit mechanism of
_ enzyme specificity comes from a change in the molec- ANNA 5 NAFF
ular surface area. The subunits of the dimer associate
in an asymmetric fashion forming a unique activator
binding site between the subunits.
10:30 Discussion and Coffee Break
10:45 ASPARTATE TRANSCARBAMYLASE, AN EX- Regulation Of Enzyme
AMPLE OF ENZYME REGULATION A t. .t
 Dr. w. N. Lipscomb C V Y
From two three-dimensional structures at 3 A resolu-
tion, and from a large body of biochemical data, some
remarks can be made about the assembly, the active
site and the regulatory processes in the allosteric en-
zyme, aspartate transcarbamylase. The enzyme C6R6 S eakers
has six catalytic polypeptide chains (C) and six regula- p
tory chains (R) in 03 symmetry. A Zn site of the Professor William N. Lipscomb
regulatory chain shows four cysteines as ligands, just Professor Thomas A. Steitz
at the boundary between C and R chains. Cytidine
triphosphate, the allosteric inhibitor, is located on the
R chain some 40 A from the catalytic site. Progress
toward a three-dimensional structure in which a sub-
strate analogue is bound will also be described. Kinet-
ics for a fragment C6 R4 indicate that about half of the 2 MARCH 3] I 1978
inhibition by cytidine triphosphate remains, in some 5 %
disagreement with a symmetry model but supporting a Fr" >_< +1
. :0 z 2:
sequential model for regulatory processes. The ques- 5 a? a 9
tion of the minimum structure required for regulation '4 (2 > T 3
will be discussed in terms of the three-dimensional 5 _g 70:,
x-ray diffraction results. ; 5 S: Q .
. . E 3. U9, Z Department of Chemistry
11.45 DISCUSSIon g E E University of Kentucky
'< 9 Lexington, Kentucky 40506