Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on June 9, 2006
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
281/23/15653    most recent
M600045200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alderwick, L. J.
Right arrow Articles by Eggeling, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alderwick, L. J.
Right arrow Articles by Eggeling, L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print April 4, 2006
J. Biol. Chem, 10.1074/jbc.M600045200
Submitted on January 3, 2006
Revised on March 31, 2006
Accepted on April 3, 2006

Identification of a novel arabinofuranosyl transferase (AftA) involved in cell wall arabinan biosynthesis in mycobacterium tuberculosis

Luke J. Alderwick, Mathias Seidel, Hermann Sahm, Gurdyal S. Besra, and Lothar Eggeling

School of Biosciences, The University of Birmingham, Birmingham B15 2TT

Corresponding Author: g.besra{at}bham.ac.uk

The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in mycobacterial species, such as Mycobacterium tuberculosis and is the target of several anti-tubercular drugs. For instance, ethambutol targets arabinogalactan biosynthesis through inhibition of the arabinofuranosyl transferases Mt-EmbA and Mt-EmbB. Following a detailed bioinformatics analysis of genes surrounding the conserved emb locus we present the identification and characterization of a novel arabinofuranosyl transferase AftA (Rv3792). The enzyme catalyzes the addition of the first key arabinofuranosyl residue from the sugar donor b-D-arabinofuranosyl-1-monophosphoryldecaprenol (DPA) to the galactan domain of the cell wall thus, “priming” the galactan for further elaboration by the arabinofuranosyl transferases. Since aftA is an essential gene in M. tuberculosis, we deleted its orthologue in Corynebacterium glutamicum to produce a slow-growing but viable mutant. Analysis of its cell wall revealed the complete absence of arabinose resulting in a truncated cell wall structure possessing only a galactan core with a concomitant loss of cell wall bound mycolates. Complementation of the mutant was fully restored to the wild type phenotype by Cg-aftA. In addition, by developing an in vitro assay using recombinant Escherichia coli expressing Mt-aftA and use of cell wall galactan as an acceptor, we demonstrated the transfer of arabinose from DPA to galactan and unlike the Mt-Emb proteins, Mt-AftA was not inhibited by ethambutol. This newly discovered glycosyltransferase represents an attractive drug target for further exploitation by chemotherapeutic intervention.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 MicrobiologyHome page
X. Meniche, C. de Sousa-d'Auria, B. Van-der-Rest, S. Bhamidi, E. Huc, H. Huang, D. De Paepe, M. Tropis, M. McNeil, M. Daffe, et al.
Partial redundancy in the synthesis of the D-arabinose incorporated in the cell wall arabinan of Corynebacterineae
Microbiology, August 1, 2008; 154(8): 2315 - 2326.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
L. Shi, R. Zhou, Z. Liu, T. L. Lowary, P. H. Seeberger, B. L. Stocker, D. C. Crick, K.-H. Khoo, and D. Chatterjee
Transfer of the First Arabinofuranose Residue to Galactan Is Essential for Mycobacterium smegmatis Viability
J. Bacteriol., August 1, 2008; 190(15): 5248 - 5255.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
R. Goude, A. G. Amin, D. Chatterjee, and T. Parish
The Critical Role of embC in Mycobacterium tuberculosis
J. Bacteriol., June 15, 2008; 190(12): 4335 - 4341.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Bhamidi, M. S. Scherman, C. D. Rithner, J. E. Prenni, D. Chatterjee, K.-H. Khoo, and M. R. McNeil
The Identification and Location of Succinyl Residues and the Characterization of the Interior Arabinan Region Allow for a Model of the Complete Primary Structure of Mycobacterium tuberculosis Mycolyl Arabinogalactan
J. Biol. Chem., May 9, 2008; 283(19): 12992 - 13000.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. Lea-Smith, K. L. Martin, J. S. Pyke, D. Tull, M. J. McConville, R. L. Coppel, and P. K. Crellin
Analysis of a New Mannosyltransferase Required for the Synthesis of Phosphatidylinositol Mannosides and Lipoarbinomannan Reveals Two Lipomannan Pools in Corynebacterineae
J. Biol. Chem., March 14, 2008; 283(11): 6773 - 6782.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
E. A. Mahrous, R. B. Lee, and R. E. Lee
A rapid approach to lipid profiling of mycobacteria using 2D HSQC NMR maps
J. Lipid Res., February 1, 2008; 49(2): 455 - 463.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
M. Belanova, P. Dianiskova, P. J. Brennan, G. C. Completo, N. L. Rose, T. L. Lowary, and K. Mikusova
Galactosyl Transferases in Mycobacterial Cell Wall Synthesis
J. Bacteriol., February 1, 2008; 190(3): 1141 - 1145.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Kaur, M. R. McNeil, K.-H. Khoo, D. Chatterjee, D. C. Crick, M. Jackson, and P. J. Brennan
New Insights into the Biosynthesis of Mycobacterial Lipomannan Arising from Deletion of a Conserved Gene
J. Biol. Chem., September 14, 2007; 282(37): 27133 - 27140.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
R. V. V. Tatituri, L. J. Alderwick, A. K. Mishra, J. Nigou, M. Gilleron, K. Krumbach, P. Hitchen, A. Giordano, H. R. Morris, A. Dell, et al.
Structural characterization of a partially arabinosylated lipoarabinomannan variant isolated from a Corynebacterium glutamicum ubiA mutant
Microbiology, August 1, 2007; 153(8): 2621 - 2629.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
S. Berg, D. Kaur, M. Jackson, and P. J Brennan
The glycosyltransferases of Mycobacterium tuberculosis--roles in the synthesis of arabinogalactan, lipoarabinomannan, and other glycoconjugates
Glycobiology, June 1, 2007; 17(6): 35R - 56R.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Seidel, L. J. Alderwick, H. L. Birch, H. Sahm, L. Eggeling, and G. S. Besra
Identification of a Novel Arabinofuranosyltransferase AftB Involved in a Terminal Step of Cell Wall Arabinan Biosynthesis in Corynebacterianeae, such as Corynebacterium glutamicum and Mycobacterium tuberculosis
J. Biol. Chem., May 18, 2007; 282(20): 14729 - 14740.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
M. Seidel, L. J. Alderwick, H. Sahm, G. S. Besra, and L. Eggeling
Topology and mutational analysis of the single Emb arabinofuranosyltransferase of Corynebacterium glutamicum as a model of Emb proteins of Mycobacterium tuberculosis
Glycobiology, February 1, 2007; 17(2): 210 - 219.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
E. Krings, K. Krumbach, B. Bathe, R. Kelle, V. F. Wendisch, H. Sahm, and L. Eggeling
Characterization of myo-Inositol Utilization by Corynebacterium glutamicum: the Stimulon, Identification of Transporters, and Influence on L-Lysine Formation
J. Bacteriol., December 1, 2006; 188(23): 8054 - 8061.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
L. J. Alderwick, L. G. Dover, M. Seidel, R. Gande, H. Sahm, L. Eggeling, and G. S. Besra
Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-D-arabinose metabolism
Glycobiology, November 1, 2006; 16(11): 1073 - 1081.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement