Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ

被引:98
作者
Forsgren, M
Attersand, A
Lake, S
Grünler, J
Swiezewska, E
Dallner, G
Climent, CL [1 ]
机构
[1] Biovitrum AB, SE-11276 Stockholm, Sweden
[2] Karolinska Inst, Dept Mol Med, Stockholm, Sweden
[3] Polish Acad Sci, Warsaw, Poland
[4] Stockholm Univ, Dept Biochem, SE-16901 Stockholm, Sweden
关键词
CoQ biosynthesis; human COQ2 gene; polyprenyl transferase; yeast mutant complementation;
D O I
10.1042/BJ20040261
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The COQ2 gene in Saccharomyces cerevisiae encodes a Coq2 (p-hydroxybenzoate:polyprenyl transferase), which is required in the biosynthetic pathway of CoQ (ubiquinone). This enzyme catalyses the prenylation of p-hydroxybenzoate with an all-trans polyprenyl group. We have isolated cDNA which we believe encodes the human homologue of COQ2 from a human muscle and liver cDNA library. The clone contained an open reading frame of length 1263 bp, which encodes a polypeptide that has sequence homology with the Coq2 homologues in yeast, bacteria and mammals. The human COQ2 gene, when expressed in yeast Coq2 null mutant cells, rescued the growth of this yeast strain in the absence of a non-fermentable carbon source and restored CoQ biosynthesis. However, the rate of CoQ biosynthesis in the rescued cells was lower when compared with that in cells rescued with the yeast COQ2 gene. CoQ formed when cells were incubated with labelled decaprenyl pyrophosphate and nonaprenyl pyrophosphate, showing that the human enzyme is active and that it participates in the biosynthesis of CoQ.
引用
收藏
页码:519 / 526
页数:8
相关论文
共 39 条
[1]  
ASHBY MN, 1992, J BIOL CHEM, V267, P4128
[2]   Disulfide bonds are generated by quinone reduction [J].
Bader, MW ;
Xie, T ;
Yu, CA ;
Bardwell, JCA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) :26082-26088
[3]  
Bateman A, 2004, NUCLEIC ACIDS RES, V32, pD138, DOI [10.1093/nar/gkp985, 10.1093/nar/gkr1065, 10.1093/nar/gkh121]
[4]   Phosphorylation of farnesol in rat liver microsomes:: Properties of farnesol kinase and farnesyl phosphate kinase [J].
Bentinger, M ;
Grünler, J ;
Peterson, E ;
Swiezewska, E ;
Dallner, G .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1998, 353 (02) :191-198
[5]   POLYPRENYL PHOSPHATES - SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP FOR A BIOSYNTHETIC SYSTEM OF SALMONELLA-ANATUM O-SPECIFIC POLYSACCHARIDE [J].
DANILOV, LL ;
DRUZHININA, TN ;
KALINCHUK, NA ;
MALTSEV, SD ;
SHIBAEV, VN .
CHEMISTRY AND PHYSICS OF LIPIDS, 1989, 51 (3-4) :191-203
[6]  
DIALAMEH GH, 1970, BIOCHEM BIOPH RES CO, V40, P1063
[7]  
Emanuelsson Olof, 2002, Brief Bioinform, V3, P361, DOI 10.1093/bib/3.4.361
[8]  
ERICSSON J, 1992, J BIOL CHEM, V267, P18708
[9]   BIOCHEMICAL, PHYSIOLOGICAL AND MEDICAL ASPECTS OF UBIQUINONE FUNCTION [J].
ERNSTER, L ;
DALLNER, G .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1995, 1271 (01) :195-204
[10]   A ubiquinone-binding site regulates the mitochondrial permeability transition pore [J].
Fontaine, E ;
Ichas, F ;
Bernardi, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (40) :25734-25740