Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120
| العنوان: | Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120 |
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| المؤلفون: | Masaru Tsunoda, Haruo Tanaka, Xiaoxue Zhang, Naomi Ohbayashi, Satoshi Ōmura, J. Jiang, Atsushi Takahashi, M.M. Hoque, Akio Takénaka, Fang Zhang, K. Suzuki |
| المصدر: | Acta Crystallographica Section D: Biological Crystallography |
| بيانات النشر: | International Union of Crystallography (IUCr), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Models, Molecular, Anti-HIV Agents, Protein Conformation, Stereochemistry, Molecular Sequence Data, Mannose, HIV Envelope Protein gp120, Crystallography, X-Ray, Mannans, Structure-Activity Relationship, chemistry.chemical_compound, Residue (chemistry), Protein structure, Bacterial Proteins, anti-HIV lectins, Structural Biology, Mannobiose, Molecule, Moiety, Amino Acid Sequence, Binding site, actinohivin, Sequence Homology, Amino Acid, high-mannose-type glycan, Hydrogen bond, General Medicine, Research Papers, Crystallography, chemistry |
| الوصف: | X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P212121 symmetry to exhibit an apparent space group P213 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O3 and O4 atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O1 atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features provide strong evidence indicating that AH is only highly specific for MB and would facilitate the highly specific affinity of AH for any glycoprotein carrying many HMTGs, such as HIV-1 gp120. |
| تدمد: | 0907-4449 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99e99422b4d50e2c07e1a83eeb6d2a5d https://doi.org/10.1107/s0907444912040498 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....99e99422b4d50e2c07e1a83eeb6d2a5d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09074449 |
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