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 C(110) in Srt1p. This suggests a significant increase in the size of the enzyme hydrophobic tunnel from approximately 1000 A(3) of E. coli UPPs to approximately 1300 A(3) required to accommodate C(80) in Rer2p and to 1700 A(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.
Poznański
Jarosław
J
Institute of Biochemistry and Biophysics PAS, ul. Pawinskiego 5a, 02-106 Warszawa, Poland.
Szkopinska
Anna
A
D000595:Amino Acid Sequence; D000818:Animals; D004122:Dimethylallyltranstransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D045782:Hemiterpenes; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000439:Pentanols / Q000378:metabolism*; D011108:Polymers / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D016415:Sequence Alignment
D045782:Hemiterpenes; D000439:Pentanols; D011108:Polymers; C009034:prenol; D004122:Dimethylallyltranstransferase