Lectins: tools for the molecular understanding of the glycocode.

Recent progress in glycobiology has revealed that cell surface oligosaccharides play an essential role in recognition events. More precisely, these saccharides may be complexed by lectins, carbohydrate-binding proteins other than enzymes and antibodies, able to recognise sugars in a highly specific manner. The ubiquity of lectin-carbohydrate interactions opens enormous potential for their exploitation in medicine. Therefore, extraordinary effort is made into the identification of new lectins as well as into the achievement of a deep understanding of their functions and of the precise mechanism of their association with specific ligands. In this review, a summary of the main features of lectins, particularly those found in legumes, will be presented with a focus on the mechanism of carbohydrate-binding. An overview of lectin-carbohydrate interactions will also be given, together with an insight into their energetics. In addition, therapeutic applications of lectins will be discussed.

[1]  A. Surolia,et al.  Mutational Analysis at Asn-41 in Peanut Agglutinin , 2001, The Journal of Biological Chemistry.

[2]  P. Crocker,et al.  Siglecs: sialic-acid-binding immunoglobulin-like lectins in cell-cell interactions and signalling. , 2002, Current opinion in structural biology.

[3]  G. Molema,et al.  TARGETING OF DRUGS TO VARIOUS BLOOD-CELL TYPES USING (NEO-)GLYCOPROTEINS, ANTIBODIES AND OTHER PROTEIN CARRIERS , 1994 .

[4]  E. Toone,et al.  Calorimetric analysis of the binding of lectins with overlapping carbohydrate-binding ligand specificities. , 1995, Biochemistry.

[5]  W. Weis,et al.  Structural basis of lectin-carbohydrate recognition. , 1996, Annual review of biochemistry.

[6]  I. Matsumoto,et al.  Mannose binding lectin gene polymorphism in patients with type I diabetes. , 2003, Human immunology.

[7]  M. Monsigny,et al.  Carbohydrate-lectin interactions assessed by surface plasmon resonance. , 2003, Biochimie.

[8]  Tumor Lectinology: At the Intersection of Carbohydrate Chemistry, Biochemistry, Cell Biology, and Oncology , 1988 .

[9]  Benjamin G Davis,et al.  Synthesis of glycoproteins. , 2002, Chemical reviews.

[10]  A. Imberty,et al.  Molecular modelling of theDolichos biflorus seed lectin and its specific interactions with carbohydrates: α-D-N-acetyl-galactosamine, Forssman disaccharide and blood group A trisaccharide , 1994, Glycoconjugate Journal.

[11]  I. Sternlieb,et al.  Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo. , 1968, The Journal of biological chemistry.

[12]  R. Dixon,et al.  Stress-Induced Phenylpropanoid Metabolism. , 1995, The Plant cell.

[13]  L. Wyns,et al.  Legume lectin structure. , 1998, Biochimica et biophysica acta.

[14]  D. Adelson,et al.  Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G M Whitesides,et al.  A trivalent system from vancomycin.D-ala-D-Ala with higher affinity than avidin.biotin. , 1998, Science.

[16]  K. Drickamer,et al.  Two distinct classes of carbohydrate-recognition domains in animal lectins. , 1988, The Journal of biological chemistry.

[17]  P. Rizkallah,et al.  High-resolution structural insights into ligand binding and immune cell recognition by human lung surfactant protein D. , 2003, Journal of molecular biology.

[18]  E. Toone,et al.  The cluster glycoside effect. , 2002, Chemical reviews.

[19]  D. Mandal,et al.  Studies of the binding specificity of concanavalin A. Nature of the extended binding site for asparagine-linked carbohydrates. , 1994, Biochemistry.

[20]  J. Calvete,et al.  Isolation of two novel mannan- and L-fucose-binding lectins from the green alga Enteromorpha prolifera: biochemical characterization of EPL-2. , 2003, Archives of biochemistry and biophysics.

[21]  R. Kelley,et al.  Thermodynamic analysis of an antibody functional epitope. , 1993, Biochemistry.

[22]  E. Toone,et al.  On the Meaning of Affinity:  Cluster Glycoside Effects and Concanavalin A , 1999 .

[23]  A. Surolia,et al.  Preparation and preliminary X‐ray studies of three acidic pH crystal forms of the anti‐T lectin from peanut (Arachis hypogaea) , 1983 .

[24]  A. Raz,et al.  Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. , 1992, Journal of the National Cancer Institute.

[25]  Yuan-chuan Lee,et al.  Carbohydrate-Protein Interactions: Basis of Glycobiology , 1995 .

[26]  B. Cavada,et al.  Thermodynamic Binding Studies of Lectins from the Diocleinae Subtribe to Deoxy Analogs of the Core Trimannoside of Asparagine-linked Oligosaccharides* , 2000, The Journal of Biological Chemistry.

[27]  T. Dam,et al.  Thermodynamic studies of lectin-carbohydrate interactions by isothermal titration calorimetry. , 2002, Chemical reviews.

[28]  W. Weis.  Lectins on a roll: the structure of E-selectin. , 1994, Structure.

[29]  R. Adar,et al.  Mutational studies of the amino acid residues in the combining site of Erythrina corallodendron lectin. , 1996, European journal of biochemistry.

[30]  R. Majhi,et al.  Lectin and serum-PSA interaction as a screening test for prostate cancer. , 2003, Clinical biochemistry.

[31]  L. Delbaere,et al.  Molecular recognition. XIV: Monte Carlo simulation of the hydration of the combining site of a Lectin , 1994 .

[32]  J. Sumner.  THE GLOBULINS OF THE JACK BEAN, CANAVALIA ENSIFORMIS Preliminary Paper , 1919 .

[33]  H. C. van der Mei,et al.  Enthalpy of interaction between coaggregating and non-coaggregating oral bacterial pairs--a microcalorimetric study. , 2003, Journal of microbiological methods.

[34]  B. Shaanan,et al.  Structures of the Erythrina corallodendron lectin and of its complexes with mono- and disaccharides. , 1998, Journal of molecular biology.

[35]  Richard D. Cummings,et al.  Thermodynamics of Carbohydrate Binding to Galectin-1 from Chinese Hamster Ovary Cells and Two Mutants. A Comparison with Four Galactose-Specific Plant Lectins† , 1996 .

[36]  A. Hamilton,et al.  Protein Surface Recognition by Synthetic Receptors: A Route to Novel Submicromolar Inhibitors for α-Chymotrypsin , 1999 .

[37]  W. Morgan,et al.  Neutralization of the Anti-H Agglutinin in Eel Serum by Simple Sugars , 1952, Nature.

[38]  R. Townsend,et al.  Binding of synthetic oligosaccharides to the hepatic Gal/GalNAc lectin. Dependence on fine structural features. , 1983, The Journal of biological chemistry.

[39]  W. Jencks,et al.  On the attribution and additivity of binding energies. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[40]  G. Bird.  Agar Gel Studies of Blood Group Specific Substances and Precipitins of Plant Origin , 1959, Vox sanguinis.

[41]  A. Surolia,et al.  Thermodynamics of the binding of galactopyranoside derivatives to the basic lectin from winged bean (Psophocarpus tetrogonolobus). , 1991, The Journal of biological chemistry.

[42]  E. Gorelik,et al.  A novel apoptotic pathway as defined by lectin cellular initiation. , 2004, Biochemical and biophysical research communications.

[43]  N. Sharon.  Bacterial lectins, cell‐cell recognition and infectious disease , 1987, FEBS letters.

[44]  N. Sharon,et al.  Lectins as cell recognition molecules. , 1989, Science.

[45]  J. Roth.  Protein N-glycosylation along the secretory pathway: relationship to organelle topography and function, protein quality control, and cell interactions. , 2002, Chemical reviews.

[46]  V. Moy,et al.  Molecular basis of the dynamic strength of the sialyl Lewis X--selectin interaction. , 2004, Chemphyschem : a European journal of chemical physics and physical chemistry.

[47]  J. Skehel,et al.  The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. , 1987, Annual review of biochemistry.

[48]  N. Sharon,et al.  Lectin-carbohydrate complexes of plants and animals: an atomic view. , 1993, Trends in biochemical sciences.

[49]  R. Miller,et al.  The macromolecular properties of peanut agglutinin. , 1978, Archives of biochemistry and biophysics.

[50]  W. Kauzmann.  Some factors in the interpretation of protein denaturation. , 1959, Advances in protein chemistry.

[51]  P. Privalov,et al.  Contribution of hydration to protein folding thermodynamics. II. The entropy and Gibbs energy of hydration. , 1993, Journal of molecular biology.

[52]  Nathan Sharon,et al.  A century of lectin research (1888–1988) , 1987 .

[53]  David R. Nadeau,et al.  Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Read,et al.  Shiga-like toxins are neutralized by tailored multivalent carbohydrate ligands , 2000, Nature.

[55]  D. S. Pilch,et al.  Thermodynamics of aminoglycoside-rRNA recognition: the binding of neomycin-class aminoglycosides to the A site of 16S rRNA. , 2002, Biochemistry.

[56]  H. de Boeck,et al.  Effect of pH on oligomeric equilibrium and saccharide-binding properties of peanut agglutinin. , 1985, Archives of biochemistry and biophysics.

[57]  L. Johnson,et al.  Design of inhibitors of glycogen phosphorylase: a study of alpha- and beta-C-glucosides and 1-thio-beta-D-glucose compounds. , 1994, Biochemistry.

[58]  Yuan-chuan Lee,et al.  Carbohydrate-binding properties of human neo-CRP and its relationship to phosphorylcholine-binding site. , 2003, Glycobiology.

[59]  R. Kerbel,et al.  Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. , 1987, Science.

[60]  A. Surolia,et al.  Legume lectin family, the 'natural mutants of the quaternary state', provide insights into the relationship between protein stability and oligomerization. , 2001, Biochimica et biophysica acta.

[61]  C. F. Brewer,et al.  Negative cooperativity associated with binding of multivalent carbohydrates to lectins. Thermodynamic analysis of the "multivalency effect". , 2002, Biochemistry.

[62]  M. Marikovsky,et al.  Clearance of senescent erythrocytes: Wheat germ agglutinin distribution on young and old human erythrocytes , 2004, Glycoconjugate Journal.

[63]  R J Read,et al.  Structure of the shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. , 1998, Biochemistry.

[64]  T. Feizi,et al.  AIDS and glycosylation. , 1990, Glycobiology.

[65]  Y. Takenaka,et al.  Galectin-3 and metastasis , 2004, Glycoconjugate Journal.

[66]  B. Cavada,et al.  The galactose-binding lectin from Vatairea macrocarpa seeds induces in vivo neutrophil migration by indirect mechanism. , 2003, The international journal of biochemistry & cell biology.

[67]  M. Hahn,et al.  Oligosaccharins: structures and signal transduction , 1994, Plant Molecular Biology.

[68]  E. Toone,et al.  Multivalency effects in protein--carbohydrate interaction: the binding of the Shiga-like toxin 1 binding subunit to multivalent C-linked glycopeptides. , 2000, The Journal of organic chemistry.

[69]  G. Ashwell,et al.  Carbohydrate-specific receptors of the liver. , 1982, Annual review of biochemistry.

[70]  S. H. Koenig,et al.  Interactions of concanavalin A with a trimannosyl oligosaccharide fragment of complex and high mannose type glycopeptides. , 1985, Biochemical and biophysical research communications.

[71]  I. Ofek,et al.  Bacterial Adhesion to Cells and Tissues , 1994, Springer US.

[72]  M. Hancock,et al.  I-type lectins. , 2002 .

[73]  A. Surolia,et al.  Crystallization and preliminary X-ray studies of the anti-T lectin from peanut (Arachis hypogaea). , 1982, Journal of molecular biology.

[74]  E. Toone.  Structure and energetics of protein-carbohydrate complexes , 1994 .

[75]  J M Sturtevant,et al.  Heat capacity and entropy changes in processes involving proteins. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[76]  C. MacKenzie,et al.  Probing the combining site of an anti-carbohydrate antibody by saturation-mutagenesis: role of the heavy-chain CDR3 residues. , 1993, Biochemistry.

[77]  U. Nilsson,et al.  Low Micromolar Inhibitors of Galectin‐3 Based on 3′‐Derivatization of N‐Acetyllactosamine , 2002 .

[78]  K. P. Murphy,et al.  Entropy in biological binding processes: Estimation of translational entropy loss , 1994, Proteins.

[79]  L M Amzel,et al.  Thermodynamics of bovine spleen galectin-1 binding to disaccharides: correlation with structure and its effect on oligomerization at the denaturation temperature. , 1998, Biochemistry.

[80]  L. Lasky.  Selectin-carbohydrate interactions and the initiation of the inflammatory response. , 1995, Annual review of biochemistry.

[81]  M. Etzler,et al.  From Structure to Activity: New Insights into the Functions of Legume Lectins , 1998 .

[82]  S. Barondes,et al.  X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution. , 1994, The Journal of biological chemistry.

[83]  George M Whitesides,et al.  Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors. , 1998, Angewandte Chemie.

[84]  Mary C. Chervenak,et al.  A Direct Measure of the Contribution of Solvent Reorganization to the Enthalpy of Binding , 1994 .

[85]  A. Surolia,et al.  Thermodynamics of Monosaccharide and Disaccharide Binding to Erythrina corallodendron Lectin* , 1996, The Journal of Biological Chemistry.

[86]  M. Kanai,et al.  Varying the Size of Multivalent Ligands: The Dependence of Concanavalin A Binding on Neoglycopolymer Length , 1997 .

[87]  W. Boyd,et al.  The Lectins: Their Present Status * , 1963, Vox sanguinis.

[88]  D. Jackson,et al.  Bovine and mouse serum beta inhibitors of influenza A viruses are mannose-binding lectins. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[89]  P. Bisch,et al.  Stochastic molecular dynamics of peanut lectin PNA complex with T-antigen disaccharide. , 2002, Journal of molecular graphics & modelling.

[90]  J. Sumner,et al.  Identification of Hemagglutinin of Jack Bean with Concanavalin A , 1936, Journal of bacteriology.

[91]  L. Sachs,et al.  Structural Difference in Sites on the Surface Membrane of Normal and Transformed Cells , 1969, Nature.

[92]  R. McEver.  Selectins: lectins that initiate cell adhesion under flow. , 2002, Current opinion in cell biology.

[93]  T. Dam,et al.  Thermodynamics of Lectin-Carbohydrate Interactions , 1997, The Journal of Biological Chemistry.

[94]  W. Hol,et al.  High-Affinity Pentavalent Ligands of Escherichia coli Heat-Labile Enterotoxin by Modular Structure-Based Design , 2000 .

[95]  T. Ng,et al.  Isolation of a novel N-acetylglucosamine-specific lectin from fresh sclerotia of the edible mushroom Pleurotus tuber-regium. , 2003, Protein expression and purification.

[96]  M. Monsigny,et al.  Characterization and biological implications of membrane lectins in tumor, lymphoid and myeloid cells. , 1988, Biochimie.

[97]  E. Berg,et al.  IFN-gamma inhibits activation-induced expression of E- and P-selectin on endothelial cells. , 1998, Journal of immunology.

[98]  A. Surolia,et al.  Molten Globule-like State of Peanut Lectin Monomer Retains Its Carbohydrate Specificity , 1999, The Journal of Biological Chemistry.

[99]  Nathan Sharon,et al.  The Lectins: Properties, Functions and Applications in Biology and Medicine , 1986 .

[100]  R. Oomen,et al.  Analysis of sequence variation among legume lectins. A ring of hypervariable residues forms the perimeter of the carbohydrate-binding site. , 1992, Journal of molecular biology.

[101]  R. Kramer,et al.  Spanning binding sites on allosteric proteins with polymer-linked ligand dimers , 1998, Nature.

[102]  T. Bisseling,et al.  Symbiotic Nitrogen Fixation. , 1995, The Plant cell.

[103]  L. Wyns,et al.  Structural basis of carbohydrate recognition by the lectin LecB from Pseudomonas aeruginosa. , 2003, Journal of molecular biology.

[104]  S. Barondes.  Bifunctional properties of lectins: lectins redefined. , 1988, Trends in biochemical sciences.

[105]  A. Surolia,et al.  Thermodynamics of monosaccharide binding to concanavalin A, pea (Pisum sativum) lectin, and lentil (Lens culinaris) lectin. , 1993, The Journal of biological chemistry.

[106]  E. Toone,et al.  Energetics of lectin-carbohydrate binding. A microcalorimetric investigation of concanavalin A-oligomannoside complexation. , 1992, The Journal of biological chemistry.

[107]  A. Surolia,et al.  Crystal Structure of the Peanut Lectin-T-Antigen Complex. Carbohydrate Specificity Generated by Water Bridges , 1997 .

[108]  I. Goldstein,et al.  Protein-carbohydrate interaction. IV. Application of the quantitative precipitin method to polysaccharide-concanavalin A interaction. , 1967, The Journal of biological chemistry.

[109]  J. Jiménez-Barbero,et al.  Chemical Biology of the Sugar Code , 2004, Chembiochem : a European journal of chemical biology.

[110]  A. Imberty,et al.  Synthesis and Conformational Analysis of a Conformationally Constrained Trisaccharide, and Complexation Properties with Concanavalin A , 1999 .

[111]  L. Baum,et al.  Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. , 2002, Current opinion in structural biology.

[112]  J. Skehel,et al.  Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. , 1994, Biochemistry.

[113]  P. Sass.  The involvement of selectins in cell adhesion, tumor progression, and metastasis. , 1998, Cancer investigation.

[114]  A. Surolia,et al.  Analyses of carbohydrate recognition by legume lectins: size of the combining site loops and their primary specificity. , 1997, Journal of molecular biology.

[115]  C. F. Brewer,et al.  Thermodynamic binding parameters of individual epitopes of multivalent carbohydrates to concanavalin a as determined by "reverse" isothermal titration microcalorimetry. , 2002, Biochemistry.

[116]  T. Irimura,et al.  A putative carbohydrate-binding domain of the lactosebindingCytisus sessilifolius anti-H(O) lectin has a similar amino acid sequence to that of thel-fucose-bindingUlex europaeus anti-H(O) lectin , 1995, Glycoconjugate Journal.

[117]  V. Hogan,et al.  Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents. , 2002, Trends in molecular medicine.

[118]  A. Surolia,et al.  Arrangement of subunits in peanut lectin. Rotation function and chemical cross-linking studies. , 1985, The Journal of biological chemistry.

[119]  A. Surolia,et al.  Structures of the complexes of peanut lectin with methyl-beta-galactose and N-acetyllactosamine and a comparative study of carbohydrate binding in Gal/GalNAc-specific legume lectins. , 1999, Acta crystallographica. Section D, Biological crystallography.

[120]  A. Tenner,et al.  Mannose binding protein (MBP) enhances mononuclear phagocyte function via a receptor that contains the 126,000 M(r) component of the C1q receptor. , 1995, Immunity.

[121]  J R Helliwell,et al.  The combination of molecular dynamics with crystallography for elucidating protein-ligand interactions: a case study involving peanut lectin complexes with T-antigen and lactose. , 2001, Acta crystallographica. Section D, Biological crystallography.

[122]  I. Goldstein,et al.  Protein-carbohydrate interaction. On the mode of bonding of aromatic moieties to concanavalin A, the phytohemagglutinin of the jack bean. , 1971, Biochemical pharmacology.

[123]  I. H. Segel,et al.  Characterization of the adenine binding sites of two Dolichos biflorus lectins. , 1992, Biochemistry.

[124]  M Vijayan,et al.  Crystal structure of peanut lectin, a protein with an unusual quaternary structure. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[125]  A. Krześlak,et al.  Differences in glycosylation of intracellular proteins between benign and malignant thyroid neoplasms. , 2003, Cancer letters.

[126]  S. Das,et al.  Binding of multivalent carbohydrates to concanavalin A and Dioclea grandiflora lectin. Thermodynamic analysis of the "multivalency effect". , 2000, The Journal of biological chemistry.

[127]  N. Sharon,et al.  Lectins: Carbohydrate-Specific Proteins That Mediate Cellular Recognition. , 1998, Chemical reviews.

[128]  G. Air,et al.  Structure of influenza virus neuraminidase B/Lee/40 complexed with sialic acid and a dehydro analog at 1.8-A resolution: implications for the catalytic mechanism. , 1994, Biochemistry.

[129]  A. Schreiber,et al.  Molecular dissection of Fc gamma receptor-mediated phagocytosis. , 1995, Immunology letters.

[130]  P. Garred,et al.  Mannose-binding lectin deficiency--revisited. , 2003, Molecular immunology.

[131]  M. Okada,et al.  The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. , 1990, The Journal of biological chemistry.

[132]  P. Privalov,et al.  Contribution of hydration to protein folding thermodynamics. I. The enthalpy of hydration. , 1993, Journal of molecular biology.

[133]  V. Malashkevich,et al.  Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. , 2000, Journal of molecular biology.

[134]  W. Boyd,et al.  Specific Precipitating Activity of Plant Agglutinins (Lectins). , 1954, Science.

[135]  C. MacKenzie,et al.  A Mutational Analysis of the Globotriaosylceramide-binding Sites of Verotoxin VT1* , 2002, The Journal of Biological Chemistry.

[136]  M Vijayan,et al.  Conformation, protein-carbohydrate interactions and a novel subunit association in the refined structure of peanut lectin-lactose complex. , 1996, Journal of molecular biology.

[137]  R. Levinsky,et al.  Molecular basis of opsonic defect in immunodeficient children , 1991, The Lancet.

[138]  H Kaltner,et al.  Involvement of laser photo-CIDNP (chemically induced dynamic nuclear polarization)-reactive amino acid side chains in ligand binding by galactoside-specific lectins in solution. , 1997, European journal of biochemistry.

[139]  Norbert Muller,et al.  Search for a realistic view of hydrophobic effects , 1990 .

[140]  D. Kilpatrick.  Animal lectins: a historical introduction and overview. , 2002, Biochimica et biophysica acta.

[141]  E. Toone,et al.  A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A , 2000 .