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Structure and function of cis-prenyl chain elongating enzymes

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Abstract

All carbon skeletons of isoprenoids, whose chain lengths vary widely from geranyl diphosphate (C10) to natural rubber (C>10,000), are synthesized by sequential condensation of isopentenyl diphosphate with an allylic diphosphate through catalytic functions of a group of enzymes commonly called “prenyltransferases.” Prenyltransferases are classified into two major groups, trans- or (E)-prenyltransferases and cis- or (Z)-prenyltransferases, according to the geometry of the prenyl chain units in the products. From the year 1987, many genes encoding trans-prenyltransferases were cloned and clearly characterized. In contrast, the structure and detailed mechanism of cis-prenyltransferase was completely unknown until the identification of a gene encoding the undecaprenyl diphosphate (UPP) synthase from Micrococcus luteus B-P 26 in 1998. Not only the primary but also the tertiary structure of the UPP synthase is quite different from that of the trans-prenyltransferases. Multiple alignment of the primary structures of cis-prenyltransferases identified from various organisms reveals five highly conserved regions. Site-directed mutagenesis of the conserved amino acid residues in UPP synthases based on the crystal structure has elucidated the basic catalytic mechanisms. Moreover, comparison of the structures of short-, medium-, and long-chain cis-prenyltransferases reveals important amino acid residues for product chain length determination, which enabled us to understand the regulation mechanism of the ultimate chain length among cis-prenyltransferases. © 2006 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 6: 194–205; 2006: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20083

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