Metabolic maps and functions of the Plasmodium falciparum apicoplast

被引:486
作者
Ralph, SA
van Dooren, GG
Waller, RF
Crawford, MJ
Fraunholz, MJ
Foth, BJ
Tonkin, CJ
Roos, DS
McFadden, GI [1 ]
机构
[1] Univ Melbourne, Sch Bot, Plant Cell Biol Res Ctr, Melbourne, Vic 3010, Australia
[2] Inst Pasteur, F-75724 Paris, France
[3] Univ British Columbia, Dept Bot, Canadian Inst Adv Res, Program Evolutionary Biol, Vancouver, BC V6T 1Z4, Canada
[4] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA
[5] Univ Penn, Genom Inst, Philadelphia, PA 19104 USA
[6] Univ London Imperial Coll Sci Technol & Med, Dept Biol Sci, London SW7 2AZ, England
关键词
D O I
10.1038/nrmicro843
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Discovery of a relict chloroplast (the apicoplast) in malarial parasites presented new opportunities for drug development. The apicoplast - although no longer photosynthetic - is essential to parasites. Combining bioinformatics approaches with experimental validation in the laborator we have identified more than 500 proteins predicted to function in the apicoplast, By comparison with plant chloroplasts, we have reconstructed several anabolic pathways for the parasite plastid that are fundamentally different to the analogous pathways in the human host and are potentially good targets for drug development. Products of these pathways seem to be exported from the apicoplast and might be involved in host-cell invasion.
引用
收藏
页码:203 / 216
页数:14
相关论文
共 184 条
[1]   Biosynthesis of terpenes:: Studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase [J].
Adam, P ;
Hecht, S ;
Eisenreich, WG ;
Kaiser, J ;
Gräwert, T ;
Arigoni, D ;
Bacher, A ;
Rohdich, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (19) :12108-12113
[2]   ISOLATION AND CHARACTERIZATION OF BIOTIN CARBOXYLASE FROM PEA-CHLOROPLASTS [J].
ALBAN, C ;
JULLIEN, J ;
JOB, D ;
DOUCE, R .
PLANT PHYSIOLOGY, 1995, 109 (03) :927-935
[3]   LytB protein catalyzes the terminal step of the 2-C-methyl-D-erythritol-4-phosphate pathway of isoprenoid biosynthesis [J].
Altincicek, B ;
Duin, EC ;
Reichenberg, A ;
Hedderich, R ;
Kollas, AK ;
Hintz, M ;
Wagner, S ;
Wiesner, J ;
Beck, E ;
Jomaa, H .
FEBS LETTERS, 2002, 532 (03) :437-440
[4]   GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli [J].
Altincicek, B ;
Kollas, AK ;
Sanderbrand, S ;
Wiesner, J ;
Hintz, M ;
Beck, E ;
Jomaa, H .
JOURNAL OF BACTERIOLOGY, 2001, 183 (08) :2411-2416
[5]   Antimalarial activity of 77 phospholipid polar head analogs:: Close correlation between inhibition of phospholipid metabolism and in vitro Plasmodium falciparum growth [J].
Ancelin, ML ;
Calas, M ;
Bompart, J ;
Cordina, G ;
Martin, D ;
Ben Bari, M ;
Jei, T ;
Druilhe, P ;
Vial, HJ .
BLOOD, 1998, 91 (04) :1426-1437
[6]   Analysis of the genome sequence of the flowering plant Arabidopsis thaliana [J].
Kaul, S ;
Koo, HL ;
Jenkins, J ;
Rizzo, M ;
Rooney, T ;
Tallon, LJ ;
Feldblyum, T ;
Nierman, W ;
Benito, MI ;
Lin, XY ;
Town, CD ;
Venter, JC ;
Fraser, CM ;
Tabata, S ;
Nakamura, Y ;
Kaneko, T ;
Sato, S ;
Asamizu, E ;
Kato, T ;
Kotani, H ;
Sasamoto, S ;
Ecker, JR ;
Theologis, A ;
Federspiel, NA ;
Palm, CJ ;
Osborne, BI ;
Shinn, P ;
Conway, AB ;
Vysotskaia, VS ;
Dewar, K ;
Conn, L ;
Lenz, CA ;
Kim, CJ ;
Hansen, NF ;
Liu, SX ;
Buehler, E ;
Altafi, H ;
Sakano, H ;
Dunn, P ;
Lam, B ;
Pham, PK ;
Chao, Q ;
Nguyen, M ;
Yu, GX ;
Chen, HM ;
Southwick, A ;
Lee, JM ;
Miranda, M ;
Toriumi, MJ ;
Davis, RW .
NATURE, 2000, 408 (6814) :796-815
[7]   Terpenoid biosynthesis from 1-deoxy-D-xylulose in higher plants by intramolecular skeletal rearrangement [J].
Arigoni, D ;
Sagner, S ;
Latzel, C ;
Eisenreich, W ;
Bacher, A ;
Zenk, MH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10600-10605
[8]   PlasmoDB:: the Plasmodium genome resource.: A database integrating experimental and computational data [J].
Bahl, A ;
Brunk, B ;
Crabtree, J ;
Fraunholz, MJ ;
Gajria, B ;
Grant, GR ;
Ginsburg, H ;
Gupta, D ;
Kissinger, JC ;
Labo, P ;
Li, L ;
Mailman, MD ;
Milgram, AJ ;
Pearson, DS ;
Roos, DS ;
Schug, J ;
Stoeckert, CJ ;
Whetzel, P .
NUCLEIC ACIDS RESEARCH, 2003, 31 (01) :212-215
[9]   Understanding in vivo carbon precursor supply for fatty acid synthesis in leaf tissue [J].
Bao, XM ;
Focke, M ;
Pollard, M ;
Ohlrogge, J .
PLANT JOURNAL, 2000, 22 (01) :39-50
[10]   INHIBITION OF CYTOPLASMIC AND ORGANELLAR PROTEIN-SYNTHESIS IN TOXOPLASMA-GONDII - IMPLICATIONS FOR THE TARGET OF MACROLIDE ANTIBIOTICS [J].
BECKERS, CJM ;
ROOS, DS ;
DONALD, RGK ;
LUFT, BJ ;
SCHWAB, JC ;
CAO, Y ;
JOINER, KA .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (01) :367-376