A Structural Model of the Membrane-Bound Aromatic Prenyltransferase UbiA from E. coli

被引:48
作者
Braeuer, Lars [1 ]
Brandt, Wolfgang [1 ]
Schulze, Diana [1 ]
Zakharova, Svetlana [1 ]
Wessjohann, Ludger [1 ]
机构
[1] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, D-06120 Halle, Germany
关键词
mutagenesis; phosphatase activity; protein models; threading; transferases;
D O I
10.1002/cbic.200700575
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 membrane-bound enzyme 4-hydroxybenzoic acid oligoprenyltransferase (ubiA) from E. coli is crucial for the production of ubiquinone, the essential electron carrier in prokaryotic and eukaryotic organisms. On the basis of previous modeling analyses, amino acids identified as important in two putative active sites (1 and 2) were selectively mutated. All mutants but one lost their ability to form geranylated hydroxybenzoate, irrespective of their being from active site 1 or 2. This suggests either that the two active sites are interrelated or that they are in fact only one site. With the aid of the experimental results and a new structure-based classification of prenylating enzymes, a relevant 3D model could be developed by threading. The new model explains the substrate specificities and is in complete agreement with the results of site-directed mutagenesis. The high similarity of the active fold of UbiA-transferase to that of S-epi-aristolochene synthase (Nicotiana tabacum), despite a low homology, allows a hypothesis on a convergent evolution of these enzymes to be formed.
引用
收藏
页码:982 / 992
页数:11
相关论文
共 77 条
[1]   Anticancer drugs from nature - natural products as a unique source of new microtubule-stabilizing agents [J].
Altmann, Karl-Heinz ;
Gertsch, Juerg .
NATURAL PRODUCT REPORTS, 2007, 24 (02) :327-357
[2]   SCOP database in 2004: refinements integrate structure and sequence family data [J].
Andreeva, A ;
Howorth, D ;
Brenner, SE ;
Hubbard, TJP ;
Chothia, C ;
Murzin, AG .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D226-D229
[3]  
[Anonymous], ANGEW CHEM
[4]  
ASHBY MN, 1992, J BIOL CHEM, V267, P4128
[5]   Metabolic engineering of isoprenoids [J].
Barkovich, R ;
Liao, JC .
METABOLIC ENGINEERING, 2001, 3 (01) :27-39
[6]   Microtubule stabilizing agents: Their molecular signaling consequences and the potential for enhancement by drug combination [J].
Bergstralh, Daniel T. ;
Ting, Jenny P. -Y. .
CANCER TREATMENT REVIEWS, 2006, 32 (03) :166-179
[7]   The Protein Data Bank [J].
Berman, HM ;
Westbrook, J ;
Feng, Z ;
Gilliland, G ;
Bhat, TN ;
Weissig, H ;
Shindyalov, IN ;
Bourne, PE .
NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242
[8]   Plant terpenoid synthases: Molecular biology and phylogenetic analysis [J].
Bohlmann, J ;
Meyer-Gauen, G ;
Croteau, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4126-4133
[9]   Biogenesis, molecular regulation and function of plant isoprenoids [J].
Bouvier, F ;
Rahier, A ;
Camara, B .
PROGRESS IN LIPID RESEARCH, 2005, 44 (06) :357-429
[10]   A proposed mechanism for the reductive ring opening of the cyclodiphosphate MEcPP, a crucial transformation in the new DXP/MEP pathway to isoprenoids, based on modeling studies and feeding experiments [J].
Brandt, W ;
Dessoy, MA ;
Fulhorst, M ;
Gao, WY ;
Zenk, MH ;
Wessjohann, LA .
CHEMBIOCHEM, 2004, 5 (03) :311-323