Structure of the Complex between a Heparan Sulfate Octasaccharide and Mycobacterial Heparin-Binding Hemagglutinin
| Autor: | Shu-Yi Lin, Cheng-Po Cheng, Shih-Han Lain, Tzu-Jui Tai, Medel Manuel L. Zulueta, Chwan-Deng Hsiao, Ping-Xi Tsai, Chia-Lin Chyan, Zhi-Geng Chen, Chiao-Chu Ku, Teng-Yi Huang, Shang-Cheng Hung, Deli Irene |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Oligosaccharides 010402 general chemistry 01 natural sciences Catalysis Virulence factor Hydrophobic effect Mycobacterium tuberculosis chemistry.chemical_compound 03 medical and health sciences Molecular recognition Lectins Pathogen chemistry.chemical_classification biology Molecular Structure General Chemistry Nuclear magnetic resonance spectroscopy Heparan sulfate General Medicine biology.organism_classification Amino acid 0104 chemical sciences 030104 developmental biology Biochemistry chemistry Heparitin Sulfate |
| Zdroj: | Angewandte Chemie. 129:4256-4260 |
| ISSN: | 0044-8249 |
| DOI: | 10.1002/ange.201612518 |
| Popis: | Heparin-binding hemagglutinin (HBHA) is a 199 amino acid virulence factor at the envelope of Mycobacterium tuberculosis that contributes to latent tuberculosis. The binding of HBHA to respiratory epithelial cells, which leads to extrapulmonary dissemination of the pathogen, is mediated by cell-surface heparan sulfate (HS). We report the structural characterization of the HBHA/HS complex by NMR spectroscopy. To develop a model for the molecular recognition, the first chemically synthesized uniformly 13 C- and 15 N-labeled HS octasaccharide and a uniformly 13 C- and 15 N-labeled form of HBHA were prepared. Residues 180-195 at the C-terminal region of HBHA show large chemical shift perturbation upon association with the octasaccharide. Molecular dynamics simulations conforming to the multidimensional NMR data revealed key electrostatic and even hydrophobic interactions between the binding partners that may aid in the development of agents targeting the binding event. |
| Databáze: | OpenAIRE |
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