title: Homodimeric hexaprenyl pyrophosphate synthase from the thermoacidophilic crenarchaeon Sulfolobus solfataricus displays asymmetric subunit structures.
abstract: Hexaprenyl pyrophosphate synthase (HexPPs) from Sulfolobus solfataricus catalyzes the synthesis of trans-C(30)-hexaprenyl pyrophosphate (HexPP) by reacting two isopentenyl pyrophosphate molecules with one geranylgeranyl pyrophosphate. The crystal structure of the homodimeric C(30)-HexPPs resembles those of other trans-prenyltransferases, including farnesyl pyrophosphate synthase (FPPs) and octaprenyl pyrophosphate synthase (OPPs). In both subunits, 10 core helices are arranged about a central active site cavity. Leu164 in the middle of the cavity controls the product chain length. Two protein conformers are observed in the S. solfataricus HexPPs structure, and the major difference between them occurs in the flexible region of residues 84 to 100. Several helices (alphaI, alphaJ, alphaK, and part of alphaH) and the associated loops have high-temperature factors in one monomer, which may be related to the domain motion that controls the entrance to the active site. Different side chain conformations of Trp136 in two HexPPs subunits result in weaker hydrophobic interactions at the dimer interface, in contrast to the symmetric pi-pi stacking interactions of aromatic side chains found in FPPs and OPPs. Finally, the three-conformer switched model may explain the catalytic process for HexPPs.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei.
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Sun
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Ko
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Kuo
authors.forename: Rey-Ting
authors.initials: RT
authors.lastname: Guo
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Chou
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Liang
authors.forename: Andrew H-J
authors.initials: AH
authors.lastname: Wang
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D048229:Sulfolobus solfataricus / Q000201:enzymology / Q000235:genetics*
chemical_list: D019843:Archaeal Proteins; D019883:Alkyl and Aryl Transferases; C036826:trans-pentaprenyltranstransferase