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Kinetic, Mechanistic, Structural and inhibitory aspects of the cis-prenyltransferase catalyzed lipid chain elongation Po-Huang Liang Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan ROC Abstract: Isoprenoids comprise a family of more than 55,000 natural products with great structural variety derived from 5-carbon isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). Allylic diphosphates such as farnesyl diphosphate (FPP) synthesized from DMAPP and IPP serve as outlet points to a great variety of products. A group of prenyltransferases catalyzing chain elongation of FPP to designated lengths by consecutive condensation reactions with specific numbers of IPP are classified as cis- and trans-types according to the stereochemistry of the double bonds formed by IPP condensation. The complete kinetics of the multiple-step IPP condensation reactions by both types of enzymes has been determined using steady-state and pre-steady-state approaches. As a result of solving their crystal structures in conjunction with biochemical studies, more understanding into their catalytic mechanisms, protein conformational changes and product chain-length determination mechanisms are gained recently. Since these prenyltransferases play important functions, potent inhibitors have been identified and their co-crystal structures have been solved for drug development. In this talk, the current knowledge particularly on the cis-prenyltranferase undecaprenyl diphosphate synthase which catalyzes consecutive condensation reactions of FPP with 8 IPP to synthesize C55 lipid is summarized. Differences between the kinetics, mechanisms, structures, and inhibitors of the cis- and trans-prenyltransferases are discussed.