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BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information
- Source :
- Molecules, Molecules, MDPI, 2020, 25 (2), pp.248. ⟨10.3390/molecules25020248⟩, Molecules, Vol 25, Iss 2, p 248 (2020), Volume 25, Issue 2, 'Molecules ', vol: 25, pages: 248-1-248-15 (2020)
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-α) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.
- Subjects :
- Models, Molecular
Burkholderia cenocepacia
Pharmaceutical Science
Gene Expression
Oligosaccharides
Fucose binding
Crystallography, X-Ray
01 natural sciences
Epitope
Analytical Chemistry
law.invention
Epitopes
law
Lectins
Drug Discovery
blood group antigen
0303 health sciences
biology
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Chemistry
Recombinant Proteins
3. Good health
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Biochemistry
Chemistry (miscellaneous)
Mannosides
Recombinant DNA
Blood Group Antigens
Molecular Medicine
Protein Binding
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
[CHIM.CRIS]Chemical Sciences/Cristallography
Humans
Antigens, Tumor-Associated, Carbohydrate
Physical and Theoretical Chemistry
Binding site
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
crystallography
030304 developmental biology
Fucose
fucosides
Binding Sites
TNF-like lectin
010405 organic chemistry
Tumor Necrosis Factor-alpha
Organic Chemistry
Lectin
Isothermal titration calorimetry
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
biology.organism_classification
Antigens, Differentiation
0104 chemical sciences
biology.protein
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules, Molecules, MDPI, 2020, 25 (2), pp.248. ⟨10.3390/molecules25020248⟩, Molecules, Vol 25, Iss 2, p 248 (2020), Volume 25, Issue 2, 'Molecules ', vol: 25, pages: 248-1-248-15 (2020)
- Accession number :
- edsair.doi.dedup.....9880cc272db88032db4ed1d3e8479bbe