PA-IIL - Revision history

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-09T09:29:44Z

Biosynthesis of ligands

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-09T09:29:03Z

Biosynthesis of ligands

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-09T09:11:01Z

Biosynthesis of ligands

Kurt Drickamer: /* Biosynthesis of ligands */

2011-10-09T09:10:29Z

Biosynthesis of ligands

Carole Weaver: /* Glycogene microarray */

2011-03-30T23:20:18Z

Glycogene microarray

Carole Weaver: /* Glycogene microarray */

2011-03-28T19:08:53Z

Glycogene microarray

Carole Weaver: /* Knockout mouse lines */

2011-03-21T19:52:42Z

Knockout mouse lines

Carole Weaver: /* Related GBPs */

2011-03-21T18:48:37Z

Related GBPs

Carole Weaver at 18:41, 2 September 2010

2010-09-02T18:41:16Z

Carole Weaver: /* Progress toward understanding this GBP paradigm */

2010-08-06T17:39:26Z

Progress toward understanding this GBP paradigm

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 === Biosynthesis of ligands ===
-Lewis a synthesis requires the addition of &alpha;1-4 fucose to the sub-terminal GlcNAc residue on a type 1 chain. Addition of the &alpha;1-4 fucose can be catalyzed by fucosyltransferase FUT3 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_600&sideMenu=true&pageType=general].
+Lewis a synthesis requires the addition of &alpha;1-4 fucose to the sub-terminal GlcNAc residue on a type 1 chain. Addition of the &alpha;1-4 fucose is catalyzed exclusively by fucosyltransferase FUT3 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_600&sideMenu=true&pageType=general].
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@@ Line 19: / Line 19: @@
 <br>
 === Biosynthesis of ligands ===
+Lewis a synthesis requires the addition of &alpha;1-4 fucose to the sub-terminal GlcNAc residue on a type 1 chain. Addition of the &alpha;1-4 fucose can be catalyzed by fucosyltransferase FUT3 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_600&sideMenu=true&pageType=general].
 <br>

@@ Line 19: / Line 19: @@
 <br>
 === Biosynthesis of ligands ===
-Lewis Y synthesis requires the addition of both &alpha;1-2 fucose to the terminal galactose residue and &alpha;1-3 fucose to the sub-terminal GlcNAc residue on a type 2 chain. Addition of the &alpha;1-2 fucose can be catalyzed by fucosyltransferases FUT1 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_598&sideMenu=true&pageType=general] and FUT2 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_599&sideMenu=true&pageType=general], while additon of the &alpha;1-3 fucose can be catalyzed by FUT4 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_601&sideMenu=true&pageType=general] and FUT9 [http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_606&sideMenu=true&pageType=general]. In lung adenocarcinomas, the FUT1 and FUT4 enzymes are primarily responsible for Lewis Y synthesis.<ref>Yang, X, Zhang, Z, Jia, S, Liu, T Wang X, and Yan, Q (2007) Overexpression of fucosyltransferase IV in A431 cell line increases cell proliferation. <i>Int. J. Biochem. Cell Biol.</i> <b>39</b>, 1722–1730</ref>
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 <br>
 === Biosynthesis of ligands ===
 === Structure ===
 PA-IIL is a tetrameric lectin. Each monomer consists of a &beta;-sandwich and contains two calcium ions that interact directly with the carbohydrate ligand. Crystal structures have been determined for PA-IIL alone, and its complex with fucose, with related monosaccharides, and with complex fucosylated oligosaccharides.

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 <br>
 === Glycogene microarray ===
-Not applicable, as the CFG microarrays only contain probes for mouse and human glycogenes.
+PA-IIL is not represented on the CFG microarrays, which only contain probes for mouse and human glycogenes.
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 <br>
 === Knockout mouse lines ===
 === Glycan array ===
 The specificity of PA-IIl and related proteins was determined through glycan array analysis (click [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_230_02102006 here] and [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_GLYCAN_v3_221_02142006# here]).

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 == Related GBPs ==
-CV-IIL, RS-IIL, BC2L-A, BC2L-B, BC2l-C
+CV-IIL [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=CV-IIL&maxresults=20 (CFG data)], RS-IIL [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=RS-IIL&cat=coreh (CFG data)], BC2L-A, BC2L-B [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=BC2L-B&maxresults=20 (CFG data)], BC2L-C [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=BC2L-C&maxresults=20 (CFG data)].
 == References ==

@@ Line 1: / Line 1: @@
-PA-IIL (Pseudomonas lectin II, LecB) is a cytoplasmic lectin produced in ''Pseudomonas aruginosa'' under the control of quorum sensing. It is a virulence factor involved in binding of human tissues such as epithelial lung of cystic fibrosis patients<ref>Imberty, A., Wimmerova, M., Mitchell, E. P. & Gilboa-Garber, N. (2004). Structures of the lectins from Pseudomonas aeruginosa: Insights into molecular basis for host glycan recognition. Microb. Infect. 6, 222-229.</ref>. The role of PA-IIL in pathogenesis has been highlighted, since interfering with PA-IIL binding site reduces the mortality of ''P. aeruginosa'' induced-pneumonia in a murine model<ref>Chemani, C., Imberty, A., de Bentzman, S., Pierre, P., Wimmerová, M., Guery, B. P. & Faure, K. (2009). Role of LecA and LecB lectins in Pseudomonas aeruginosa induced lung injury and effect of carbohydrates ligands. Infect.  Immun. 77, 2065-2075.</ref>.  The paradigm is unique among glycan-binding proteins (GBPs) in that it contains two cations ions in the carbohydrate binding site that result in unusual high affinity for the carbohydrate target<ref>Loris, R., Tielker, D., Jaeger, K.-E. & Wyns, L. (2003). Structural basis of carbohydrate recognition by the lectin LecB from Pseudomonas aeruginosa. J. Mol. Biol. 331, 861-870.</ref><ref name="test 1">Mitchell, E., Houles, C., Sudakevitz, D., Wimmerova, M., Gautier, C., Pérez, S., Wu, A. M., Gilboa-Garber, N. & Imberty, A. (2002). Structural basis for oligosaccharide-mediated adhesion of  Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Nature Struct. Biol. 9, 918-921.</ref><ref>Mitchell, E. P., Sabin, C., Šnajdrová, L., Pokorná, M., Perret, S., Gautier, C., Hofr, C., Gilboa-Garber, N., Koča, J., Wimmerová, M. & Imberty, A. (2005). High affinity fucose binding of Pseudomonas aeruginosa lectin PA-IIL: 1.0 Å resolution crystal structure of the complex combined with thermodynamics and computational chemistry approaches. Proteins: Struct. Funct. Bioinfo. 58, 735-748.</ref>. The preferred glycan ligand of PA-IIL is the trisaccharide Lewis a<ref name="test 2">Perret, S., Sabin, C., Dumon, C., Pokorná, M., Gautier, C., Galanina, O., Ilia, S., Bovin, N., Nicaise, M., Desmadril, M., Gilboa-Garber, N., Wimmerova, M., Mitchell, E. P. & Imberty, A. (2005). Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa. Biochem. J. 389, 325-332.</ref>. PA-IIL-like lectins have been characterized in other opportunistic bacteria such as ''Ralstonia solanacearum''<ref>Sudakevitz, D., Kostlanova, N., Blatman-Jan, G., Mitchell, E. P., Lerrer, B., Wimmerova, M., Katcof, f. D. J., Imberty, A. & Gilboa-Garber, N. (2004). A new Ralstonia solanacearum high affinity mannose-binding lectin RS-IIL structurally resembling the Pseudomonas aeruginosa fucose-specific lectin PA-IIL. Mol. Microbiol. 52, 691-700.</ref>, ''Chromobacterium violaceum''<ref name="Pokorna 11">Pokorná, M., Cioci, G., Perret, S., Rebuffet, E., Kostlánová, N., Adam, J., Gilboa-Garber, N., Mitchell, E. P., Imberty, A. & Wimmerová, M. (2006). Unusual entropy driven affinity of Chromobacterium violaceum lectin CV-IIL towards fucose and mannose. Biochemistry 45, 7501-7510.</ref>, and ''Burkholderia cenocepacia''<ref>Lameignere, E., Malinovská, L., Sláviková, M., Duchaud, E., Mitchell, E. P., Varrot, A., Šedo, O., Imberty, A. & Wimmerová, M. (2008). Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia. Biochem. J. 411, 307-318.</ref><ref>Lameignere, E., Shiao, T. C., Roy, R., Wimmerová, M., Dubreuil, F., Varrot, A. & Imberty, A. (2010). Structural basis of the affinity for oligomannosides and analogs displayed by BC2L-A, a Burkholderia cenocepacia soluble lectin. Glycobiology 20, 87-98.</ref>, albeit with some variations in the fine specificity. Starting from the results obtained with the help of CFG tools, major efforts are devoided in collaboration with carbohydrate chemists in order to design anti-bacterial new glyco-derived compounds that bind to PA-IIL with high affinity<ref>Imberty, A., Chabre, Y. M. & Roy, R. (2008). Glycomimetics and glycodendrimers as high affinity microbial antiadhesins. Chemistry 14, 7490-7499.</ref>.
+PA-IIL (Pseudomonas lectin II, LecB) is a cytoplasmic lectin produced in ''Pseudomonas aruginosa'' under the control of quorum sensing. It is a virulence factor involved in binding of human tissues such as epithelial lung of cystic fibrosis patients<ref name="Imberty 2004">Imberty, A., Wimmerova, M., Mitchell, E. P. & Gilboa-Garber, N. (2004). Structures of the lectins from Pseudomonas aeruginosa: Insights into molecular basis for host glycan recognition. Microb. Infect. 6, 222-229.</ref>. The role of PA-IIL in pathogenesis has been highlighted, since interfering with PA-IIL binding site reduces the mortality of ''P. aeruginosa'' induced-pneumonia in a murine model<ref name="Chemani 2009">Chemani, C., Imberty, A., de Bentzman, S., Pierre, P., Wimmerová, M., Guery, B. P. & Faure, K. (2009). Role of LecA and LecB lectins in Pseudomonas aeruginosa induced lung injury and effect of carbohydrates ligands. Infect.  Immun. 77, 2065-2075.</ref>.  The paradigm is unique among glycan-binding proteins (GBPs) in that it contains two cationic ions in the carbohydrate binding site that result in unusual high affinity for the carbohydrate target<ref>Loris, R., Tielker, D., Jaeger, K.-E. & Wyns, L. (2003). Structural basis of carbohydrate recognition by the lectin LecB from Pseudomonas aeruginosa. J. Mol. Biol. 331, 861-870.</ref><ref name="test 1">Mitchell, E., Houles, C., Sudakevitz, D., Wimmerova, M., Gautier, C., Pérez, S., Wu, A. M., Gilboa-Garber, N. & Imberty, A. (2002). Structural basis for oligosaccharide-mediated adhesion of  Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Nature Struct. Biol. 9, 918-921.</ref><ref>Mitchell, E. P., Sabin, C., Šnajdrová, L., Pokorná, M., Perret, S., Gautier, C., Hofr, C., Gilboa-Garber, N., Koča, J., Wimmerová, M. & Imberty, A. (2005). High affinity fucose binding of Pseudomonas aeruginosa lectin PA-IIL: 1.0 Å resolution crystal structure of the complex combined with thermodynamics and computational chemistry approaches. Proteins: Struct. Funct. Bioinfo. 58, 735-748.</ref>. The preferred glycan ligand of PA-IIL is the trisaccharide Lewis a<ref name="test 2">Perret, S., Sabin, C., Dumon, C., Pokorná, M., Gautier, C., Galanina, O., Ilia, S., Bovin, N., Nicaise, M., Desmadril, M., Gilboa-Garber, N., Wimmerova, M., Mitchell, E. P. & Imberty, A. (2005). Structural basis for the interaction between human milk oligosaccharides and the bacterial lectin PA-IIL of Pseudomonas aeruginosa. Biochem. J. 389, 325-332.</ref>. PA-IIL-like lectins have been characterized in other opportunistic bacteria such as ''Ralstonia solanacearum''<ref>Sudakevitz, D., Kostlanova, N., Blatman-Jan, G., Mitchell, E. P., Lerrer, B., Wimmerova, M., Katcof, f. D. J., Imberty, A. & Gilboa-Garber, N. (2004). A new Ralstonia solanacearum high affinity mannose-binding lectin RS-IIL structurally resembling the Pseudomonas aeruginosa fucose-specific lectin PA-IIL. Mol. Microbiol. 52, 691-700.</ref>, ''Chromobacterium violaceum''<ref name="Pokorna 11">Pokorná, M., Cioci, G., Perret, S., Rebuffet, E., Kostlánová, N., Adam, J., Gilboa-Garber, N., Mitchell, E. P., Imberty, A. & Wimmerová, M. (2006). Unusual entropy driven affinity of Chromobacterium violaceum lectin CV-IIL towards fucose and mannose. Biochemistry 45, 7501-7510.</ref>, and ''Burkholderia cenocepacia''<ref>Lameignere, E., Malinovská, L., Sláviková, M., Duchaud, E., Mitchell, E. P., Varrot, A., Šedo, O., Imberty, A. & Wimmerová, M. (2008). Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia. Biochem. J. 411, 307-318.</ref><ref>Lameignere, E., Shiao, T. C., Roy, R., Wimmerová, M., Dubreuil, F., Varrot, A. & Imberty, A. (2010). Structural basis of the affinity for oligomannosides and analogs displayed by BC2L-A, a Burkholderia cenocepacia soluble lectin. Glycobiology 20, 87-98.</ref>, albeit with some variations in the fine specificity. Starting from the results obtained with the help of CFG tools, major efforts are devoided in collaboration with carbohydrate chemists in order to design anti-bacterial new glyco-derived compounds that bind to PA-IIL with high affinity<ref>Imberty, A., Chabre, Y. M. & Roy, R. (2008). Glycomimetics and glycodendrimers as high affinity microbial antiadhesins. Chemistry 14, 7490-7499.</ref>.
 == CFG Participating Investigators contributing to the understanding of this paradigm ==
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 == Progress toward understanding this GBP paradigm ==
 This section documents what is currently known about PA-IIL, its carbohydrate ligand(s), and how they interact to mediate cell communication.
 === Carbohydrate ligands ===
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 === Biological roles of GBP-ligand interaction ===
+PA-IIL, a virulence factor that binds human tissues such as epithelial lung of cystic fibrosis patients<ref name="Imberty 2004"/>, has roles in pathogenesis <ref name="Chemani 2009"/>.
 <br>