Mechanistic, kinetic and inhibitory studies of a short-chain and a long-chain cis-type prenyltransferases from M. tuberculosis.
Date Issued
2006
Date
2006
Author(s)
Chen, Ling-Yuan
DOI
en-US
Abstract
Isoprenoids are widely distributed natural polymers containing isopentenyl pyrophosphate (IPP) as building block. The biosyntheses of isoprenoids are carried out by a group of enzymes called prenyltransferases which catalyze the head to tail condensation between IPP and farnesyl pyrophosphate (FPP) to make linear long-chain products. In bacteria, by using all-trans FPP, the C55 undecaprenyl pyrophosphate (UPP) generated by UPP synthase (UPPs) serves as a lipid carrier to transport lipid II across the bacterial cell membrane for peptidoglycan synthesis of the cell wall. However, in M. tuberculosis, a novel short-chain FPP synthase (FPPs) was found to catalyze the condensation between 10-carbon geranyl pyrophosphate and IPP to form a cis double bond. From this ω,E,Z-FPP, a C50 long-chain decaprenyl pyrophosphate (DPP) is synthesized by the decaprenyl pyrophosphate synthase (DPPs) as the lipid carrier in M. tuberculosis. In this thesis, I describe the mechanistic and kinetic caracterization of this novel FPPs as well as the DPPs. For developing anti- M. tuberculosis drug, we used the crystal structure of UPPs as a template and performed computer screening to search for the small molecule inhibitors of the M. tuberculosis FPPs and DPPs.
Subjects
結核桿菌
異戊二烯焦磷酸轉移酶
cis-type prenyltransferases
FPPs
DPPs
SDGs
Type
other
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