title: Product chain-length determination mechanism of Z,E-farnesyl diphosphate synthase.
abstract: cis-Prenyltransferases catalyze the consecutive condensation of isopentenyl diphosphate (IPP) with allylic prenyl diphosphates, producing Z,E-mixed prenyl diphosphate. The Mycobacterium tuberculosis Z,E-farnesyl diphosphate synthase Rv1086 catalyzes the condensation of one molecule of IPP with geranyl diphosphate to yield Z,E-farnesyl diphosphate and is classified as a short-chain cis-prenyltransferase. To elucidate the chain-length determination mechanism of the short-chain cis-prenyltransferase, we introduced some substitutive mutations at the characteristic amino acid residues of Rv1086. Among the mutants constructed, L84A showed a dramatic change of catalytic function to synthesize longer prenyl chain products than that of wild type, indicating that Leu84 of Rv1086 plays an important role in product chain-length determination. Mutagenesis at the corresponding residue of a medium-chain cis-prenyltransferase, Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase also resulted in the production of different prenyl chain length from the intrinsic product, suggesting that this position also plays an important role in product chain-length determination for medium-chain cis-prenyltransferases.
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Noike
authors.forename: Takanori
authors.initials: T
authors.lastname: Ambo
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Seiji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kurokawa
authors.forename: Sebabrata
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Dean C
authors.initials: DC
authors.lastname: Crick
authors.forename: Tanetoshi
authors.initials: T
authors.lastname: Koyama
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D002384:Catalysis; D017124:Conserved Sequence; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000235:genetics; D051228:Geranyltranstransferase / Q000737:chemistry* / Q000235:genetics; D007930:Leucine / Q000737:chemistry* / Q000235:genetics; D016982:Micrococcus luteus / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D017433:Protein Structure, Secondary / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D019883:Alkyl and Aryl Transferases; C412569:Rv1086 protein, Mycobacterium tuberculosis; D004122:Dimethylallyltranstransferase; D051228:Geranyltranstransferase; D007930:Leucine
references.citation: J Biol Chem. 2001 Jul 27;276(30):28459-64
references.pmid: 11346651
references.citation: Biochim Biophys Acta. 2003 Feb 20;1625(3):291-5
references.pmid: 12591616
references.citation: J Biol Chem. 1996 Mar 29;271(13):7820-8
references.pmid: 8631826
references.citation: J Mol Biol. 2008 Aug 1;381(1):129-40
references.pmid: 18597781
references.citation: J Biochem. 2000 Dec;128(6):917-22
references.pmid: 11098133
references.citation: Nat Prod Rep. 2003 Feb;20(1):111-8
references.pmid: 12636086
references.citation: Biochem J. 1972 Mar;127(1):11-25
references.pmid: 4627447
references.citation: J Biol Chem. 2000 Jul 28;275(30):22876-81
references.pmid: 10816587
references.citation: J Biochem. 2003 Dec;134(6):819-26
references.pmid: 14769870
references.citation: Chem Rev. 1998 Jun 18;98(4):1263-1276
references.pmid: 11848932
references.citation: J Bacteriol. 1999 Jan;181(2):483-92
references.pmid: 9882662
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4337-42
references.pmid: 11287651
references.citation: FEMS Microbiol Lett. 1994 Jun 15;119(3):255-62
references.pmid: 8050708
references.citation: Biochim Biophys Acta. 1982 Sep 14;712(3):716-8
references.pmid: 7126635
references.citation: Methods Enzymol. 1985;110:130-44
references.pmid: 2991702
references.citation: J Biol Chem. 2001 Dec 14;276(50):47474-82
references.pmid: 11581264
references.citation: Biosci Biotechnol Biochem. 1999 Oct;63(10):1671-6
references.pmid: 10586494
references.citation: FEBS J. 2006 Feb;273(3):647-57
references.pmid: 16420487
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417