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

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dc.citation.issue3
dc.citation.volume284
dc.contributor.authorLubkowski, Jacek
dc.contributor.authorDurbin, Sarah V.
dc.contributor.authorSilva, Mariana C. C. [UNIFESP]
dc.contributor.authorFarnsworth, David
dc.contributor.authorGildersleeve, Jeffrey C.
dc.contributor.authorOliva, Maria Luiza V. [UNIFESP]
dc.contributor.authorWlodawer, Alexander
dc.coverageHoboken
dc.date.accessioned2020-07-17T14:03:10Z
dc.date.available2020-07-17T14:03:10Z
dc.date.issued2017
dc.description.abstractLectins 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 panelen
dc.description.abstractin 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 K-d = 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. Database Structural data are available in the PDB under the accession numbers 5T50, 5T52, 5T55, 5T54, 5T5L, 5T5J, 5T5P, and 5T5O.en
dc.description.affiliationNCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA
dc.description.affiliationNCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipFAPESP (PD-BEPE)
dc.description.sponsorshipU.S. Department of Energy, Office of Science, Office of Basic Energy Sciences
dc.description.sponsorshipIDFAPESP: 2009/53766-5
dc.description.sponsorshipIDFAPESP: 2012/06366-4
dc.description.sponsorshipIDFAPESP: 2014/22649-1
dc.description.sponsorshipIDFAPESP (PD-BEPE): 2014/22649-1
dc.description.sponsorshipIDU.S. Department of Energy, Office of Science, Office of Basic Energy Sciences: W-31-109-Eng-38
dc.format.extent429-450
dc.identifierhttp://dx.doi.org/10.1111/febs.13989
dc.identifier.citationFebs Journal. Hoboken, v. 284, n. 3, p. 429-450, 2017.
dc.identifier.doi10.1111/febs.13989
dc.identifier.issn1742-464X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55199
dc.identifier.wosWOS:000393601800008
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofFebs Journal
dc.rightsAcesso aberto
dc.subjectcancer cell growth inhibitionen
dc.subjectcarbohydrate bindingen
dc.subjectcrystal structureen
dc.subjectlectinen
dc.subjectTn antigenen
dc.titleStructural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growthen
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