Expression cloning of cholesterol α-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori

Lee, Heeseob; Kobayashi, Motohiro; Wang, Ping; Nakayama, Jun; Seeberger, Peter H.; Fukuda, Minoru

doi:10.1016/j.bbrc.2006.08.145

Cited by 44 publications

(40 citation statements)

References 24 publications

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“…Interestingly, both α1,3/4-FucT and CHLαGcT lack a transmembrane domain (Ge et al 1997;Lee et al 2006), suggesting that both are soluble proteins. Recently, Ma et al (2003) suggested that α1,3/4-FucT could associate with the inner membrane through C-terminal regions rich in positively charged and hydrophobic residues functioning as a membrane anchor.…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol α-glucosyltransferase (CHLαGcT), which we and others molecularly cloned from H. pylori, is the glycosyltransferase that transfers glucose from UDP-glucose to a carbon atom at the third position of cholesterol with an α1,3-linkage (Lee et al 2006; Lebrun et al 2006). High conservation of CHLαGcT amino acid sequence among Helicobacter species suggests that this enzyme plays an important role in Helicobacter growth (Lee et al 2008).…”

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confidence: 97%

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Membrane-associated Activation of Cholesterol α-Glucosyltransferase, an Enzyme Responsible for Biosynthesis of Cholesteryl-α-d-Glucopyranoside in Helicobacter pylori Critical for Its Survival

Hoshino¹,

Tsuchida²,

Kametani³

et al. 2011

J Histochem Cytochem.

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Helicobacter pylori ( H. pylori) is the causative pathogen underlying gastric diseases such as chronic gastritis and gastric cancer. Previously, the authors revealed that α1,4-linked N-acetylglucosamine-capped O-glycan (αGlcNAc) found in gland mucin suppresses H. pylori growth and motility by inhibiting catalytic activity of cholesterol α-glucosyltransferase (CHLαGcT), the enzyme responsible for biosynthesis of the major cell wall component cholesteryl-α-d-glucopyranoside (CGL). Here, the authors developed a polyclonal antibody specific for CHLαGcT and then undertook quantitative ultrastructural analysis of the enzyme’s localization in H. pylori. They show that 66.3% of CHLαGcT is detected in the cytoplasm beneath the H. pylori inner membrane, whereas 24.7% is present on the inner membrane. In addition, 2.6%, 5.0%, and 1.4% of the protein were detected in the periplasm, on the outer membrane, and outside microbes, respectively. By using an in vitro CHLαGcT assay with fractionated H. pylori proteins, which were used as an enzyme source for CHLαGcT, the authors demonstrated that the membrane fraction formed CGL, whereas other fractions did not. These data combined together indicate that CHLαGcT is originally synthesized in the cytoplasm of H. pylori as an inactive form and then activated when it is associated with the cell membrane. This article contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Membrane-associated Activation of Cholesterol α-Glucosyltransferase, an Enzyme Responsible for Biosynthesis of Cholesteryl-α-d-Glucopyranoside in Helicobacter pylori Critical for Its Survival

Hoshino¹,

Tsuchida²,

Kametani³

et al. 2011

J Histochem Cytochem.

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“…All proteins had the EX 7 E motif, which is a putative active site of glycosyltransferases in the C-terminal half 22,23,35 ( Figure 1). …”

Section: H Muridarum a K I Dw I E N K D Q L E E M K I K Y K Q S A Q mentioning

confidence: 99%

“…[22][23][24] αCgT is a unique enzyme that belongs to the glycosyltransferase family 4 (also named GT1_UGDG-like family) and shows similarities to some bacterial diacylglycerol-α-glycosyltransferase enzymes, but not to plant steryl-β-glycosyltransferases. 42 52 39 28 49 56 42 9 9 9 10 8 5 WP_000237258.1 38 50 41 24 46 100 45 5 7 7 8 8 7 AB665412 37 48 28 21 47 79 43 8 7 9 10 8 6 AB665414 52 44 42 36 52 83 37 7 6 11 6 8 9 AB665413 43 53 40 27 45 48 49 9 6 11 11 9 8 WP_011577534.1 45 45 36 29 48 81 35 8 7 9 …”

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confidence: 99%

Cholesterol‐α‐glucosyltransferase gene is present in most Helicobacter species including gastric non‐Helicobacter pylori helicobacters obtained from Japanese patients

et al. 2017

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Background Non‐Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa‐associated lymphoid tissue lymphoma. Cholesteryl‐α‐glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol‐α‐glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl‐α‐glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. Materials and Methods Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. Results αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. Conclusions All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes.

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“…4). Two independent groups reported by two independent groups on the cloning of cholesteryl a-glucosyl transferase (25,26). And a study showing that intrinsic a-glucosylation of cholesterol abrogates the phagocytosis of H. pylori and subsequent Tcell activation (27).…”

Section: The Biological Background Of Anti-helicobacter Pylorimentioning

confidence: 99%

Development of Novel Glycosyl Donors for 1,2-<i>cis</i> Glycosylation Reaction for Amino Sugar and Synthesis of anti-<i>Helicobacter pylori</i> Oligosaccharide

Manabe

Ishii

Ito

2008

TIGG

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Despite advances in synthetic carbohydrate chemistry, the 1,2-cis-selective glycosylation reaction of 2-deoxy-2-amino sugars has not progressed during the last three decades. For such glycosylations, 2-azide glycosyl donors have been extensively employed, notwithstanding di‹cul-ties in their preparation and moderate selectivities. Herein, we report on a highly 1,2-cis-selective trans-carbamate sugar donor, which can be readily prepared in high yields. Furthermore, the utility of the novel cis-selective glycosyl donor for preparing complex oligosaccharides is demonstrated through the eŠective synthesis of an antiHelicobacter pylori hexasaccharide.

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Expression cloning of cholesterol α-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori

Cited by 44 publications

References 24 publications

Membrane-associated Activation of Cholesterol α-Glucosyltransferase, an Enzyme Responsible for Biosynthesis of Cholesteryl-α-d-Glucopyranoside in Helicobacter pylori Critical for Its Survival

Membrane-associated Activation of Cholesterol α-Glucosyltransferase, an Enzyme Responsible for Biosynthesis of Cholesteryl-α-d-Glucopyranoside in Helicobacter pylori Critical for Its Survival

Cholesterol‐α‐glucosyltransferase gene is present in most Helicobacter species including gastric non‐Helicobacter pylori helicobacters obtained from Japanese patients

Development of Novel Glycosyl Donors for 1,2-<i>cis</i> Glycosylation Reaction for Amino Sugar and Synthesis of anti-<i>Helicobacter pylori</i> Oligosaccharide

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