HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 13, 9973-9982, March 30, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/13/9973    most recent M610285200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, H.-Y. Articles by Lin, C.-H. Search for Related Content PubMed PubMed Citation Articles by Sun, H.-Y. Articles by Lin, C.-H. Social Bookmarking                      What's this?

Structure and Mechanism of Helicobacter pylori Fucosyltransferase

A BASIS FOR LIPOPOLYSACCHARIDE VARIATION AND INHIBITOR DESIGN^*

Han-Yu Sun¹, Sheng-Wei Lin¹, Tzu-Ping Ko¹, Jia-Fu Pan, Chia-Ling Liu, Chun-Nan Lin, Andrew H.-J. Wang^¶||2, and Chun-Hung Lin^¶3

From the Institute of Biochemical Sciences, National Taiwan University, Taipei 10642 and the Institute of Biological Chemistry, the ^¶Genomics Research Center, and the ^||National Core Facility of High-Throughput Protein Crystallography, Academia Sinica, No.128 Academia Road Section 2, Nan-Kang, Taipei 11529, Taiwan

Helicobacter pylori 1,3-fucosyltransferase (FucT) is involved in catalysis to produce the Lewis x trisaccharide, the major component of the bacteria's lipopolysaccharides, which has been suggested to mimic the surface sugars in gastric epithelium to escape host immune surveillance. We report here three x-ray crystal structures of FucT, including the FucT·GDP-fucose and FucT·GDP complexes. The protein structure is typical of the glycosyltransferase-B family despite little sequence homology. We identified a number of catalytically important residues, including Glu-95, which serves as the general base, and Glu-249, which stabilizes the developing oxonium ion during catalysis. The residues Arg-195, Tyr-246, Glu-249, and Lys-250 serve to interact with the donor substrate, GDP-fucose. Variations in the protein and ligand conformations, as well as a possible FucT dimer, were also observed. We propose a catalytic mechanism and a model of polysaccharide binding not only to explain the observed variations in H. pylori lipopolysaccharides, but also to facilitate the development of potent inhibitors.

Received for publication, November 3, 2006 , and in revised form, January 12, 2007.

The atomic coordinates and structure factors (codes 2NZW, 2NZX, and 2NZY) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Academia Sinica and the National Science Council, Taiwan (Grant NSC-94-3112-B-001-010-Y to A. H.-J. W. and Grant NSC-94-2113-M-001-0028 to C. H. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Figs. S1–S3.

¹ These authors contributed equally to this work.

² To whom correspondence may be addressed. Tel.: 886-2-2788-1981; Fax: 886-2-2788-2043; E-mail: ahjwang{at}gate.sinica.edu.tw. ³ To whom correspondence may be addressed. Tel.: 886-2-2789-0110; Fax: 886-2-2651-4705; E-mail: chunhung{at}gate.sinica.edu.tw.

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

This article has been cited by other articles:

				S. Shetterly, F. Jost, S. R. Watson, R. Knegtel, B. A. Macher, and E. H. Holmes Site-specific Fucosylation of Sialylated Polylactosamines by {alpha}1,3/4-Fucosyltransferases-V and -VI Is Defined by Amino Acids Near the N Terminus of the Catalytic Domain J. Biol. Chem., August 24, 2007; 282(34): 24882 - 24892. [Abstract] [Full Text] [PDF]