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