Precise bacterial polyprenol length control fails in Saccharomyces cerevisiae

A comparison of amino acid sequences of yeast Rer2p and Srt1p Z-prenyltransferases shows that the spatial organization of their substrate tunnels agrees with that determined by X-ray for the E.coli undecaprenyl diphosphate synthase (UPPs). The observed trend in the maxima of product length distribution shifted from C-55 in UPPs to C-80 in Rer2p and to C110 in Srt1p. This suggests a significant increase in the size of the enzyme hydrophobic tunnel from similar to 1000 angstrom(3) of E. coli UPPs to similar to 1300 angstrom(3) required to accomodate C-80 in Rer2p and to 1700 angstrom(3) required to accomodate C-80 in Rer2p and to 1700 angstrom(3) for C-110 in Srt1p. Moreover, Srt1p products reaching C-290 indicate the failure of a strict bacterial-like chain length control. On the basis of E. coli UPPs crystallographic structure the yeast Rer2p model was constructed. In the model three amino acid residues inserted into the sequence corresponding to the "floor" region of the tunnel extends the bottom loop what results in the required increase of the tunnel volume. Moreover, thermal fluctuations of this loop occasionally create a hole in the tunnel floor, making escape of polyprenol omega end out of the tunnel possible what switches off the control mechanism of product length thereby allowing a practically unlimited elongation process leading to an exponential distribution of longer chain polyprenols exponential distribution of longer chain polyprenols (c) 2007 Wiley Periodicals, Inc.