High-resolution structure of a new Tn antigen-binding lectin from Vatairea macrocarpa and a comparative analysis of Tn-binding legume lectins

Sousa, Bruno; Filho, J. C. Silva; Kumar, Prashant; Pereira, Ronniery Ilario; Lyskowski, Andrzej Franciszek; Rocha, B.A.M.; Delatorre, P.; Bezerra, G.A.; Nagano, Celso Shiniti; Gruber, Karl; Cavada, Benildo S.

doi:10.1016/j.biocel.2014.12.002

Cited by 26 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Attention is given to their application in biotechnology, because they can be used for medical diagnostic (Mislovičová et al ., ) and are the main material in the manufacture of tools like microarrays, biosensors, biomarkers, and affinity chromatography (Dan et al , ). Lectins are also important tools to glycan characterization in cells (Sousa et al , ) and act as anti‐insect and antimicrobial agents (Hamid et al , ). Leguminous lectins are the most characterized, showing structural similarity, but diversity in carbohydrate binding specificity and biological activities (Cavada et al , ).…”

Section: Introductionmentioning

confidence: 99%

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia

Nascimento

Silva

et al. 2015

J of Molecular Recognition

Self Cite

View full text Add to dashboard Cite

Andira anthelmia (tribe Dalbergieae), a plant from Brazilian Amazon, possesses a seed lectin that was purified by affinity chromatography in sepharose-mannose. This novel Dalbergieae lectin, named AAL, agglutinated rabbit erythrocytes treated with trypsin. The hemagglutinating activity of AAL was maintained after incubation at a wide range of temperature (40 to 70 °C) and pH, was shown to be dependent on divalent cations, and was inhibited by d-mannose and d-sucrose. AAL showed an electrophoretic profile in sodium dodecyl sulfate-polyacrylamide gel electrophoresis similar to other lectins of the tribe Dalbergieae, presenting a double band of molecular weight with approximately 20 kDa and other minor bands of 17, 15, and 13 kDa, being the smaller fragment glycosylated. AAL injected by intravenous route in mice showed antinociceptive activity in two behavioral tests (writhing and formalin). In the writhing test induced by acetic acid, AAL showed inhibitory effect at 0.01 mg/kg (68%), 0.1 mg/kg (46%) and 1 mg/kg (74%). In the formalin test, AAL (0.1 mg/kg) inhibited by 48% the licking time in the inflammatory phase, an effect that was recovered by the lectin association with mannose. In conclusion, AAL presents analgesic effect involving the lectin domain via peripheral mechanisms of inflammatory nociception. This activity highlights the importance of lectins as tools to be used for understanding the interaction of protein-carbohydrate in processes associated to inflammatory pain. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

Section: Introductionmentioning

confidence: 99%

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia

Nascimento

Silva

et al. 2015

J of Molecular Recognition

Self Cite

View full text Add to dashboard Cite

show abstract

“…Two structures of the Vateirea macrocarpa lectin (VML) complexed with the GalNAcα1‐O‐Ser have been previously determined. The PDB coordinate set http://www.rcsb.org/pdb/search/structidSearch.do?structureId=4U36 represents the 1.4 Å structure of a complex with the natural lectin, whereas the coordinates http://www.rcsb.org/pdb/search/structidSearch.do?structureId=4XTP were obtained with recombinant protein at 1.97 Å resolution. These two structures are virtually identical (r.m.s.d.…”

Section: Resultsmentioning

confidence: 99%

“…of 1. 34 A for 219 C a pairs. Another structure of a tetrameric lectin complexed with the same antigen was determined at 2.…”

Section: Comparisons Of the Tn Antigen-binding Sitesmentioning

confidence: 99%

Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth

et al. 2017

View full text Add to dashboard Cite

Lectins have been used at length for basic research and clinical applications. New insights into the molecular recognition properties enhance our basic understanding of carbohydrate-protein interactions and aid in the design/development of new lectins. In this study, we used a combination of cell based assays, glycan microarrays, and X-ray crystallography to evaluate the structure and function of the recombinant Bauhinia forficata lectin (BfL). The lectin was shown to be cytostatic for several cancer cell lines included in the NCI-60 panel; in particular, it inhibited growth of melanoma cancer cells (LOX IMVI) by over 95%. BfL is dimeric in solution and highly specific for binding of oligosaccharides and glycopeptides with terminal N-acetylgalactosamine (GalNAc). BfL was found to have especially strong binding (apparent Kd = 0.5-1.0 nM) to the tumor associated Tn antigen. High-resolution crystal structures were determined for the ligand-free lectin, as well as for its complexes with three Tn glycopeptides, globotetraose, and the blood group A antigen. Extensive analysis of the eight crystal structures and comparison to structures of related lectins revealed several unique features of GalNAc recognition. Of special note, the carboxylate group of Glu126, lining the glycan-binding pocket, forms H-bonds with both the N-acetyl of GalNAc and the peptide amido group of Tn antigens. Stabilization provided by Glu126 is described here for the first time for any GalNAc-specific lectin. Taken together, the results provide new insights into the molecular recognition of carbohydrates and provide a structural understanding that will enable rational engineering of BfL for a variety of applications.

show abstract

“…[8,9] together with the geometries found in X-ray structures for these determinants when bound to some biologicalt argets. [21,[25][26][27][28] Newmanp rojections of Cb-O1 bond are shown. b) Superposition of the Tn antigen moiety a-O-GalNAc-Thr bound to SM3 (in green) and 237-mAb (in yellow; mAb = monoclonal antibody).…”

Section: Methodsmentioning

confidence: 99%

Deciphering the Non‐Equivalence of Serine and Threonine O‐Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti‐MUC1 Antibody

et al. 2015

View full text Add to dashboard Cite

The structural features of MUC1-like glycopeptides bearing the Tn antigen (a-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. Fort he a-O-GalNAc-Ser derivative,t he glycosidic linkage adopts ah igh-energy conformation, barely populated in the free state.This unusual structure (also observed in an a-SGalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar.T he selection of ap articular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts,w hich force ac hange in the orientation of the sugar moiety.T his seems to be unfeasible in the a-O-GalNAc-Thr glycopeptide owingtothe more limited flexibility of the side chain imposed by the methyl group.O ur data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes.T hese features providei nsight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies.

show abstract

High-resolution structure of a new Tn antigen-binding lectin from Vatairea macrocarpa and a comparative analysis of Tn-binding legume lectins

Cited by 26 publications

References 45 publications

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia

Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth

Deciphering the Non‐Equivalence of Serine and Threonine O‐Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti‐MUC1 Antibody

Contact Info

Product

Resources

About